Home One-pot synthesis of 3,4-dihydro-3-hydroxyisochroman-1-one and evaluation of acetal derivatives as antibacterial and antifungal agents
Article Open Access

One-pot synthesis of 3,4-dihydro-3-hydroxyisochroman-1-one and evaluation of acetal derivatives as antibacterial and antifungal agents

  • Gautam M. Patel and Pradeep T. Deota EMAIL logo
Published/Copyright: October 2, 2014
Download Article (PDF)
Heterocyclic Communications
From the journal Heterocyclic Communications Volume 20 Issue 5

Abstract

A one-pot synthesis of 3,4-dihydro-3-hydroxyisochroman-1-one (lactol) 3 by oxidation of indene using tungstic acid-hydrogen peroxide is reported. The synthesized lactol was converted into acetal derivatives 5a–h, which were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, Streptococcus pyogenes (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative) strains, and antifungal activity against Candida albicans and Aspergillus niger by broth dilution method. The compounds show potent activity against S. aureus in comparison with ampicillin and exhibit modest antifungal activity.

Keywords: acetals; antibacterial; antifungal; 3,4-dihydro-3-hydroxyisochroman-1-one; lactol

Introduction

The lactol scaffold is a core structural unit in various biologically active compounds such as callipeltoside A [1], ginkgolides [2, 3], dysidiolide [4], cladocorans A and B [5], acuminolide [6], spongianolide A [7], manoalide [8], cacospongionolide B2 [9], and peniolactol [10]. Lactols are also employed as important synthetic precursors to several compounds such as illudalic acid [11], benzopyran-1-ones [12], caronaldehyde [13], mevalonate, and mevaldate [14].

The lactol unit has been assembled via different routes such as photosensitized oxygenation of furan, oxidative cleavage of olefins or diols, followed by cyclization using various reagents like sodium metaperiodate [11], aqueous potassium hydroxide [13], trifluoroacetic acid [14], and ozonolysis [15] in several steps. Schöpf and Kühne [16] have been the first to report the synthesis of lactol 3 in four steps. Abe and colleagues [17–19] have also synthesized lactol 3 by photooxygenation in three steps from indene, and its crystal structure has been subsequently reported by Valente et al. [20].

Earlier, our group has demonstrated the synthetic utility of tungstic acid-hydrogen peroxide in t-butanol to furnish the corresponding trans-diol of (Z,Z)-cycloocta-1,5-diene in 65% yield [21]. The treatment of endo-dicyclopentadiene with this reagent combination in t-butanol unexpectedly resulted in the formation of polycyclic oxetanes [22]. Our continued interest in the dihydroxylation of olefins prompted us to explore the reaction of indene (1) with a tungstic acid-hydrogen peroxide mixture in order to prepare its trans-diol, which is an important intermediate for indinavir (Crixivan), an HIV protease inhibitor [23]. However, this reaction resulted in the formation of not only racemic indan-trans-1,2-diol 2 but also racemic lactol 3 (Scheme 1). This serendipitous formation of lactol encouraged us to further investigate this reaction.

Scheme 1
Scheme 1

Results and discussion

Because certain 4- and 5-oxoacids exist as cyclic lactols or pseudoacids [20], it is clear that 3 is formed as a result of cleavage of indene followed by in situ cyclization of the intermediate 2-carboxyphenylethanal. To ascertain the source of the lactol 3, the experiments were designed as follows. Initially, it was thought that indan-trans-1,2-diol 2 could be oxidized to 3 via intermediacy of 2-carboxyphenylethanal, but the treatment of 2 with tungstic acid-hydrogen peroxide at 30°C in t-butanol left it unchanged even after 14 h. It was then contemplated that the cis-diol of indene could be the source of 3. Thus, indan-cis-1,2-diol 4 was prepared by a reported method [24] and treated with tungstic acid-hydrogen peroxide. This reaction gave a mixture of lactol 3 and trans-diol 2 in 28% and 63% yields, respectively (Scheme 1). A similar conversion of 4 to 2 in the presence of nickel at 60°C has been reported [25]. It should be noted that the present method (Scheme 1) furnishes 2 from 4 in better yield (63%) under milder conditions.

These observations also implied that 4 could be transformed into lactol 3 via oxidative cleavage followed by cyclization under the reaction conditions. A similar cleavage of 2 does not take place during the reaction, perhaps due to the trans geometry of the hydroxyl groups. To the best of our knowledge, this one-pot synthesis of 3,4-dihydro-3-hydroxyisochroman-1-one 3 from indene 1 under such mild conditions is described here for the first time.

Lactol derivatives show a wide variety of biological activities [4–11]. These interesting biological properties prompted us to prepare the acetal derivatives 5a–h (Scheme 2) and examine their antimicrobial activity. The cyclic lactols are known to coexist with open-chain structures having free aldehyde functionality that can react with alcohols to form acetals [20]. Various acetal derivatives of lactol 5a–h were synthesized to examine the effect of spacer groups on their biological potency. The catalyst quantity and the reaction temperature play an important role in the formation of acetal derivatives. It was observed that lactol 3 underwent dehydration to 6 by increasing either the temperature or the catalyst quantity (>12.5 mol%) (Scheme 2).

Scheme 2
Scheme 2

All synthesized compounds (2, 3, and 5a–h) were tested for their in vitro antimicrobial activities. The minimum inhibitory concentration (MIC) of the compounds were recorded against two Gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes), two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and fungi (Candida albicans and Aspergillus niger) by broth dilution method [26, 27]. Standard antibacterial drug ampicillin and antifungal drug griseofulvin were also screened under identical conditions for comparison. Individual MIC values of all the compounds and for the standards are listed in Table 1. The results reveal that all compounds show significant antibacterial activity. All compounds show good activity against S. aureus (Gram-positive bacteria). Derivatives 5d and 5e are potent against E. coli (MIC=62.5 μg/mL) and P. aeruginosa (MIC=62.5 μg/mL), respectively.

Table 1

Results of antibacterial and antifungal screening of compounds 2, 3, and 5a–h.

CompoundMIC (μg/mL)
E. coli

MTCC 443		P. aeruginosa

MTCC 1688		S. aureus

MTCC 96		S. pyogenes

MTCC 442		C. albicans

MTCC 227		A. niger

MTCC 282
2200500200250500>1000
3125250100100>1000500
5a2502002002001000>1000
5b20025010010010001000
5c2002502002001000>1000
5d62.5100200200500>1000
5e20062.5250250500500
5f200200250250>1000200
5g250250100100>1000250
5h250200250250>10001000
Ampicillin100100250100––
Griseofulvin––––500100

MICs of ampicillin and griseofulvin are used as standards for comparison and hence are in bold.

The antifungal screening data show that a few compounds are potent against fungal strains. Compounds 2, 5d, and 5e are equipotent against C. albicans in comparison with griseofulvin.

Conclusion

A one-pot synthesis of 3,4-dihydro-3-hydroxyisochroman-1-one (lactol) 3 from indene 1 is reported along with its probable route of formation. Various acetal derivatives 5a–h were prepared and tested for biological activity. All products exhibit moderate to good antibacterial and antifungal activity.

Experimental

IR spectra were obtained using KBr pellets on a Shimadzu 8400S FTIR spectrometer. 1H NMR spectra (400 MHz) and 13C NMR spectra (100 MHz) were determined on a Bruker-400 FT NMR spectrometer in CDCl3. Mass spectra were obtained on a Shimadzu QP-5050 mass spectrometer. Column chromatography was carried out using Acme’s silica gel (60–120 mesh size) and eluting with light petroleum and ethyl acetate mixtures. Thin-layer chromatography (TLC) was performed using Acme’s silica gel for TLC and spots were visualized with the iodine vapor.

Synthesis of indan-trans-1,2-diol (2) and 3,4-dihydro-3-hydroxyisochroman-1-one (3)

To a stirred solution of indene (5 mL, 43 mmol) in t-butanol (25 mL) was added a suspension of tungstic acid (0.5 g) and hydrogen peroxide (30%, 140 mmol). The mixture was stirred for 14 h at room temperature (∼30°C). After completion of the reaction, as monitored by TLC, the mixture was filtered through a celite pad to remove the suspended catalyst. The filtrate was diluted with water (20 mL) and extracted with ethyl acetate (4×25 mL). The combined organic extracts were washed with water (15 mL), brine (10 mL), and dried over anhydrous sodium sulfate. Removal of solvent and column chromatography of the residue furnished the indan-trans-1,2-diol (2, 2.10 g, 39%) and 3,4-dihydro-3-hydroxyisochroman-1-one (3, 0.90 g, 16%). Prolonged reaction periods did not appreciably alter the product ratio.

2,3-Dihydro1H-indan-trans-1,2-diol (2)

White crystalline solid; mp 156–160°C; IR (νmax, cm-1): 3226, 2911, 2849, 1559, 1477, 1458, 1354, 1057, 746, 645; 1H NMR: δH 2.74 (dd, 1H, CH2 geminal, J1 = 15.5 Hz, J2 = 7.5 Hz), 3.18 (dd, 1H, CH2 geminal, J1 = 15.5 Hz, J2 = 7.5 Hz), 4.25 (m, 1H, CH-OH), 5.04 (d, 1H, Ar-CH-OH, J = 5.6 Hz), 4.88 and 4.86 (s, 2H, OH, both exchange with D2O), 7.32 (m, 4H, aromatic H); 13C NMR: δC 37.7, 80.6, 81.1, 123.9, 124.3, 126.3, 127.4, 138.9, 143.1. MS (EI): m/z 150 (M+). Anal. Calcd for C9H10O2: C, 71.98; H, 6.71. Found: C, 71.80; H, 6.74.

3,4-Dihydro-3-hydroxyisochroman-1-one (3)

White crystalline solid; mp 95°C; IR (νmax, cm-1): 3276, 2923, 1702, 1603, 1439, 1393, 1133, 1067, 735. 1H NMR: δH 1.70 (broad s, 1H, OH, exchanges with D2O), 3.15 (dd, 1H, CH2, J1 = 16.6 Hz, J2 = 4.6 Hz), 3.35 (dd, 1H, CH2, J1 = 16.6 Hz, J2 = 4.6 Hz), 5.95 (t, 1H, CH-OH, J = 4.8 Hz), 7.54 (m, 4H, aromatic H); 13C NMR: δC 34.2, 96.2, 124.7, 127.9, 128.6, 130.2, 134.5, 136.6, 165.5; MS (EI): m/z 164 (M+). Anal. Calcd for C9H8O3: C, 65.85; H, 4.91. Found: C, 65.78; H, 4.84.

Synthesis of indan-trans-1,2-diol (2) and 3,4-dihydro-3-hydroxyisochroman-1-one (3) from cis-diol (4)

The reaction was conducted and the products isolated as described above. Column chromatography furnished the indan-trans-1,2-diol (2, 0.63 g, 63%) and 3,4-dihydro-3-hydroxyisochroman-1-one (3, 0.31 g, 28%).

Synthesis of acetal derivatives 5a–h

To a mixture of the lactol 3 (3.05 mmol) and an alcohol (3.65 mmol) in dry toluene (20 mL) was added concentrated H2SO4 (0.4 mL) at room temperature under stirring for 5 h. After completion of the reaction (TLC), the solvent was removed and the mixture was neutralized with saturated solution of sodium bicarbonate and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, and dried over anhydrous sodium sulfate. Removal of solvent followed by chromatography of the residue furnished 5a–h.

3-Ethoxy-3,4-dihydroisochroman-1-one (5a)

Light yellow liquid; yield 72%; IR (νmax, cm-1): 2946, 2912, 2834, 1729, 1628, 1464, 1310, 1274, 1104, 1092, 738; 1H NMR: δH 1.20 (t, 3H, OCH2CH3, J = 6.9 Hz), 3.15 (dd, 1H, CH2, J1 = 16.2 Hz, J2 = 4.8 Hz), 3.35 (dd, 1H, CH2, J1 = 16.2 Hz, J2 = 4.8 Hz), 3.70 (m, 1H, OCH2CH3), 3.98 (m, 1H, OCH2CH3), 5.55 (t, 1H, CH-OR, J = 4 Hz), 7.52 (m, 4H, aromatic H); 13C NMR: δC 15.3, 33.7, 65.3, 101.1, 125.0, 127.7, 128.3, 129.9, 134.1, 136.6, 164.2; MS (EI): m/z 192 (M+). Anal. Calcd for C11H12O3: C, 68.74; H, 6.29. Found: C, 68.76; H, 6.23.

3,4-Dihydro-3-propoxyisochroman-1-one (5b)

Light yellow liquid; yield 78%; IR (νmax, cm-1): 2964, 2933, 2879, 1728, 1610, 1462, 1379, 1271, 1016, 910, 731; 1H NMR: δH 0.88 (t, 3H, OCH2CH2CH3, J = 7.2 Hz), 1.60 (m, 2H, OCH2CH2CH3), 3.12 (dd, 1H, CH2, J1 = 16.3 Hz, J2 = 4.4 Hz), 3.31 (dd, 1H, CH2, J1 = 16.3 Hz, J2 = 4.4 Hz), 3.59 (m, 1H, OCH2CH2CH3), 3.91 (m, 1H, OCH2CH2CH3), 5.57 (t, 1H, CH-OCH2CH2CH3, J = 4.4 Hz), 7.54 (m, 4H, aromatic H); 13C NMR: δC 15.3, 22.6, 33.4, 71.1, 101.0, 124.9, 127.5, 128.1, 129.9, 133.9, 136.5, 164.2; MS (EI): m/z 206 (M+). Anal. Calcd for C12H14O3: C, 69.88; H, 6.84. Found: C, 69.79; H, 6.88.

3-Butoxy-3,4-dihydroisochroman-1-one (5c)

Light yellow liquid; yield 74%; IR (νmax, cm-1): 2958, 2935, 2874, 1728, 1610, 1460, 1379, 1271, 1128, 1053, 732, 692; 1H NMR: δH 0.89 (t, 3H, OCH2CH2CH2CH3, J = 7.2 Hz), 1.30 (m, 2H, OCH2CH2CH2CH3), 1.60 (m, 2H, OCH2CH2CH2CH3), 3.11 (dd, 1H, CH2, J1 = 18.2 Hz, J2 = 4.4 Hz), 3.30 (dd, 1H, CH2, J1 = 18.2 Hz, J2 = 4.4 Hz), 3.62 (m, 1H, OCH2CH2CH2CH3), 3.97 (m, 1H, OCH2CH2CH2CH3), 5.56 (t, 1H, CH-OCH2CH2CH2CH3, J = 4.1 Hz), 7.52 (m, 4H, aromatic H); 13C NMR: δC 13.7, 19.0, 31.3, 33.4, 69.3, 101.0, 124.9, 127.5, 128.1, 129.9, 133.9, 136.4, 164.2; MS (EI): m/z 220 (M+). Anal. Calcd for C13H16O3: C, 70.89; H, 7.32. Found: C, 70.81; H, 7.26.

3,4-Dihydro-3-(pentyloxy)isochroman-1-one (5d)

Light yellow liquid; yield 71%; IR (νmax, cm-1): 2956, 2933, 2872, 1732, 1620, 1460, 1383, 1271, 1136, 1072, 732; 1H NMR: δH 0.86 (t, 3H, OCH2(CH2)3CH3, J = 6.4 Hz), 1.28 (m, 4H, OCH2CH2(CH2)2CH3), 1.56 (m, 2H, OCH2CH2(CH2)2CH3), 3.10 (dd, 1H, CH2, J1 = 17.4 Hz, J2 = 4.4 Hz), 3.29 (dd, 1H, CH2, J1 = 17.4 Hz, J2 = 4.4 Hz), 3.60 (m, 1H, OCH2(CH2)3CH3), 3.94 (m, 1H, OCH2(CH2)3CH3), 5.55 (t, 1H, CH-OCH2(CH2)3CH3, J = 4 Hz), 7.48 (m, 4H, aromatic H); 13C NMR: δC 12.3, 22.5, 27.9, 29.0, 34.2, 69.6, 101.0, 123.4, 127.5, 128.1, 129.9, 133.9, 136.5, 164.2; MS (EI): m/z 234 (M+). Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.68; H, 7.71.

3,4-Dihydro-3-(octyloxy)isochroman-1-one (5e)

Light yellow liquid; yield 76%; IR (νmax, cm-1): 3018, 2928, 1723, 1612, 1464, 1320, 1244, 1045, 794, 689; 1H NMR: δH 0.86 (t, 3H, OCH2(CH2)6CH3, J = 6.4 Hz), 1.25 (m, 10H, OCH2CH2(CH2)5CH3), 1.55 (m, 2H, OCH2CH2(CH2)5CH3), 3.09 (dd, 1H, CH2, J1 = 17.1 Hz, J2 = 4.4 Hz), 3.28 (dd, 1H, CH2, J1 = 17.1 Hz, J2 = 4.4 Hz), 3.59 (m, 1H, OCH2(CH2)6CH3), 3.93 (m, 1H, OCH2(CH2)6CH3), 5.54 (t, 1H, CH-OCH2(CH2)6CH3, J = 3.6 Hz), 7.52 (m, 4H, aromatic H); 13C NMR: δC 14.0, 22.6, 25.8, 29.1, 29.2, 29.2, 31.7, 33.4, 69.6, 101.0, 124.9, 127.5, 128.1, 129.8, 133.8, 136.5, 164.0; MS (EI): m/z 276 (M+). Anal. Calcd for C17H24O3: C, 73.88; H, 8.75. Found: C, 73.82; H, 8.78.

3-(Dodecyloxy)-3,4-dihydroisochroman-1-one (5f)

Light yellow liquid; yield 78%; IR (νmax, cm-1): 2968, 2931, 2868, 1728, 1637, 1487, 1251, 1045, 792, 688; 1H NMR: δH 0.89 (t, 3H, OCH2(CH2)10CH3, J = 6.8 Hz), 1.26 (m, 18H, OCH2CH2(CH2)9CH3), 1.60 (m, 2H, OCH2CH2(CH2)9CH3), 3.12 (dd, 1H, CH2, J1 = 16.6 Hz, J2 = 4.8 Hz), 3.31 (dd, 1H, CH2, J1 = 16.6 Hz, J2 = 4.8 Hz), 3.62 (m, 1H, OCH2(CH2)10CH3), 3.96 (m, 1H, OCH2(CH2)10CH3), 5.56 (t, 1H, CH-OCH2(CH2)10CH3, J = 4 Hz), 7.54 (m, 4H, aromatic H); 13C NMR: δC 14.1, 22.6, 25.7, 29.3, 29.4, 29.4, 29.5, 29.5, 29.6, 29.6, 31.8, 32.7, 62.9, 107.0, 125.5, 128.5, 129.5, 134.8, 136.4, 144.6, 162.2; MS (EI): m/z 332 (M+). Anal. Calcd for C21H32O3: C, 75.86; H, 9.70. Found: C, 75.78; H, 9.66.

3,4-Dihydro-3-(tetradecyloxy)isochroman-1-one (5g)

White crystalline solid; yield 80%; IR (νmax, cm-1): 3020, 2938, 1720, 1637, 1487, 1330, 1251, 1045, 794, 688; 1H NMR: δH 0.89 (t, 3H, OCH2(CH2)12CH3, J = 6.8 Hz), 1.28 (m, 22H, OCH2CH2(CH2)11CH3), 1.58 (m, 2H, OCH2CH2(CH2)11CH3), 3.12 (dd, 1H, CH2, J1 = 16.6 Hz, J2 = 4.4 Hz), 3.31 (dd, 1H, CH2, J1 = 16.6 Hz, J2 = 4.4 Hz), 3.62 (m, 1H, OCH2(CH2)12CH3), 3.95 (m, 1H, OCH2(CH2)12CH3), 5.56 (t, 1H, CH-OCH2(CH2)12CH3, J = 4.4 Hz), 7.52 (m, 4H, aromatic H); 13C NMR: δC 14.1, 22.7, 25.8, 29.3, 29.3, 29.3, 29.5, 29.5, 29.5, 29.6, 29.6, 29.7, 31.9, 33.4, 69.7, 101.0, 124.9, 127.5, 128.1, 129.9, 133.9, 136.4, 164.1. MS (EI): m/z 360 (M+). Anal. Calcd for C23H36O3: C, 76.62; H, 10.06. Found: C, 76.58; H, 10.10.

3-(Hexadecyloxy)-3,4-dihydroisochroman-1-one (5h)

White crystalline solid; yield 78%; IR (νmax, cm-1): 3090, 2941, 2837, 1720, 1637, 1487, 1251, 1045, 794, 688; 1H NMR: δH 0.89 (t, 3H, OCH2(CH2)14CH3, J = 6.9 Hz), 1.26 (m, 26H, OCH2CH2(CH2)13CH3), 1.57 (m, 2H, OCH2CH2(CH2)13CH3), 3.11 (dd, 1H, CH2, J1 = 16.6 Hz, J2 = 4.4 Hz), 3.30 (dd, 1H, CH2, J1 = 16.6 Hz, J2 = 4.4 Hz), 3.61 (m, 1H, OCH2(CH2)14CH3), 3.96 (m, 1H, OCH2(CH2)14CH3), 5.56 (t, 1H, CH-OCH2(CH2)14CH3, J = 4 Hz), 7.54 (m, 4H, aromatic H); 13C NMR: δC 14.1, 22.7, 25.7, 25.8, 29.3, 29.3, 29.4, 29.4, 29.5, 29.5, 29.6, 29.6, 29.7, 31.9, 32.8, 33.4, 69.7, 101.0, 124.9, 127.5, 128.1, 129.9, 133.9, 136.5, 164.1; MS (EI): m/z 388 (M+). Anal. Calcd for C25H40O3: C, 77.27; H, 10.38. Found: C, 77.22; H, 10.30.

1H-Isochromen-1-one (6)

[28] White crystalline solid; mp 46°C; IR (νmax, cm-1): 2962, 1732, 1610, 1462, 1246, 1008, 731; 1H NMR: δH 6.52 (d, 1H, CH=CH-O, J = 5.6 Hz), 7.28 (d, 1H, CH=CH-O, J = 5.2 Hz), 7.62 (m, 4H, aromatic H); 13C NMR: δC 107.0, 121.8, 125.5, 128.6, 129.7, 134.8, 136.4, 144.7, 162.2.

Antibacterial assay

Compounds 2, 3, and 5a–h were screened for their antibacterial activity against Gram-positive bacteria [S. aureus (MTCC-96) and S. pyogenes (MTCC-442)] and Gram-negative bacteria [Escherichia coli (MTCC-443) and P. aeruginosa (MTCC-1688)]. All MTCC cultures were collected from the Institute of Microbial Technology, Chandigarh, India. The activity of compounds was determined as per National Committee for Clinical Laboratory Standards (NCCLS) protocol using Mueller Hinton broth (Becton Dickinson, Franklin Lakes, NJ, USA). Compounds were screened for their antibacterial activity as primary screening in five sets against S. aureus, S. pyogenes, E. coli, and P. aeruginosa at different concentrations of 1000, 500, and 250 μg/mL. The compounds found to be active in primary screening were similarly diluted to obtain 200, 125, 100, 62.5, 50, 25, and 12.5 μg/mL concentrations for secondary screening to test in a second set of dilution against all microorganisms. Inoculum size for test strain was adjusted to 106 colony forming unit (CFU)/mL by comparing the turbidity (turbidimetric method). Mueller Hinton broth was used as nutrient medium to grow and dilute the compound suspension for test bacteria. DMSO (2%) was used as a diluent/vehicle to obtain the desired concentration of synthesized compounds and standard drugs to test against standard microbial strains. The compounds were diluted to 2000-μg/mL concentration as a stock solution. The control tube containing no antibiotic was immediately subcultured (before inoculation) by spreading a loopful evenly over a quarter of plate of medium suitable for the growth of test organisms. The tubes were then put for incubation at 37°C for 24 h for bacteria. Suspensions (10 μg/mL) were further inoculated on an appropriate media, and growth was noted after 24 and 48 h. The highest dilution (lowest concentration) preventing appearance of turbidity was considered as MIC (μg/mL), i.e., the amount of growth from the control tube before incubation (which represents the original inoculum) was compared. A set of tubes containing only seeded broth and solvent controls were maintained under identical conditions to ensure that the solvent had no influence on strain growth. The result was greatly affected by the size of the inoculum. The test mixture should contain 106 CFU/mL organisms. The standard drug used in the present study was ampicillin for evaluating antibacterial activity.

Antifungal assay

Compounds 2, 3, and 5a–h were also tested for antifungal activity in primary screening in five sets against C. albicans and A. niger at various concentrations of 1000, 500, and 250 μg/mL. Compounds found to be active in the primary screening were similarly diluted to obtain 200-, 125-, 100-, 62.5-, 50-, 25-, and 12.5-μg/mL concentrations for a secondary screening to test in a second set of dilution against all microorganisms. For fungal growth, in the present protocol, Sabourauds dextrose broth was used at 28°C in aerobic condition for 48 h. Griseofulvin was used as a standard drug for antifungal activity.

Corresponding author: Pradeep T. Deota, Faculty of Technology and Engineering, Applied Chemistry Department, The Maharaja Sayajirao University of Baroda, Vadodara 390001, India, e-mail:

Acknowledgments

G.M.P. thanks UGC, New Delhi, India, for the award of a research fellowship under the RFSMS scheme.

References

[1] Evans, D. A.; Hu, E.; Tedrow, J. S. An aldol-based approach to the asymmetric synthesis of l-callipeltose, the deoxyamino sugar of l-callipeltoside A. Org. Lett. 2001, 3, 3133–3136 [and references cited therein].Search in Google Scholar

[2] Stromgaard, K.; Nakanishi, K. Chemistry and biology of terpene trilactones from Ginkgo Biloba. Angew. Chem. Int. Ed. 2004, 43, 1640–1658.Search in Google Scholar

[3] Nakanishi, K. Terpene trilactones from Gingko biloba: from ancient times to the 21st century. Bioorg. Med. Chem. 2005, 13, 4987–5000.Search in Google Scholar

[4] Boukouvalas, J.; Cheng, Y. X.; Robichaud, J. Total synthesis of (+)-dysidiolide. J. Org. Chem. 1998, 63, 228–229.Search in Google Scholar

[5] Yamada, Y.; Miyaoka, H.; Yamanishi, M.; Kajiwara, Y. Total synthesis of cladocorans A and B: a structural revision. J. Org. Chem. 2003, 68, 3476–3479.Search in Google Scholar

[6] Lee, I.-S.; Ma, X.; Chai, H; Madulid, D. A.; Lamont, R. B.; Cordell, G. A.; Pezzuto, J. M.; Kinghorn, A. D. Novel cytotoxic labdane diterpenoids from Neouvaria acuminatissima. Tetrahedron 1995, 51, 21–28.Search in Google Scholar

[7] He, H.; Kulanthaivel, P.; Baker, B. J. New cytotoxic sesterterpenes from the marine sponge Spongia sp. Tetrahedron Lett. 1994, 35, 7189–7192.Search in Google Scholar

[8] De Silva, E. D.; Scheuer, P. J. Manoalide, an antibiotic sesterterpenoid from the marine sponge Luffariella variabilis (Polejaeff). Tetrahedron Lett. 1980, 21, 1611–1614.Search in Google Scholar

[9] De Rosa, S.; Crispino, A.; De Giulio, A.; Iodice, C.; Pronzato, R.; Zavodnik, N. Cacospongionolide B, a new sesterterpene from the sponge Fasciospongia cavernosa. J. Nat. Prod. 1995, 58, 1776–1780.Search in Google Scholar

[10] Saeed, A. A short total synthesis of rac-peniolactol. Monatsh Chem. 2003, 134, 457–463.Search in Google Scholar

[11] Shen, J.; Ling, Q.; Huang, Y.; Zhou, Y.; Cai, Z.; Xiong, B.; Zhang, Y.; Maa, L.; Wang, X.; Li, X.; Li, J. Illudalic acid as a potential LAR inhibitor: synthesis, SAR, and preliminary studies on the mechanism of action. Bioorg. Med. Chem. 2008, 16, 7399–7409.Search in Google Scholar

[12] Hauser, F. M.; Baghdanov, V. M. A new procedure for regiospecific syntheses of benzopyran-1-ones. J. Org. Chem. 1988, 53, 4676–4681.Search in Google Scholar

[13] Tkachev, A. V.; Kolesnik, V. D.; Rukavishnikov, A. V. Synthesis of (-)-caronaldehyde from (+)-3-carene. Mendeleev Commun. 1995, 5, 179–180.Search in Google Scholar

[14] Kondratov, I. S.; Gerus, I. I.; Kukhar, V. P.; Manoilenko, O. V. New synthetic approach to mevalonate and mevaldate fluoroanalogues. Tetrahedron: Asymmetry 2007, 18, 1918–1925.Search in Google Scholar

[15] Rousha, W. R.; Roth, J.; Madoux, F.; Hodderb, P. Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds. Bioorg. Med. Chem. Lett. 2008, 18, 2628–2632.Search in Google Scholar

[16] Schöpf, C.; Kühne, R. Notiz über 2-oxy-hydrindon-(1). Chem. Ber. 1950, 83, 390–394.Search in Google Scholar

[17] Einaga, H.; Nojima, M.; Abe, M. Photooxygenation (electron transfer) of silyl enol ethers derived from 1-indanone: silyl group and medium effects on the competitive formation of 3-siloxy-1,2-dioxetane and α-peroxy ketone. Main Group Metal Chem. 1999, 22, 539–544.Search in Google Scholar

[18] Einaga, H.; Nojima, M.; Abe, M. Photooxygenation (1O2) of silyl enol ethers derived from indan-1-ones: competitive formation of tricyclic 3-siloxy-1,2-dioxetane and silylperoxy ketone. J. Chem. Soc. Perkin Trans. 1 1999, 17, 2507–2512.Search in Google Scholar

[19] Abe, M.; Inakazu, T.; Munakata, J.; Nojima, M. 18O-Tracer studies of Fe(II)-induced decomposition of 1,2,4-trioxolanes (ozonides) derived from cyclopentenes and indenes. Inner-sphere electron transfer reduction of the peroxide linkage. J. Am. Chem. Soc. 1999, 121, 6556–6562.Search in Google Scholar

[20] Valente, E. J.; Fuller, J. E.; Ball, J. D. Pseudoacids I. 4- and 5-Oxoacids. Acta Cryst. 1998, B54, 162–173.Search in Google Scholar

[21] Deota, P. T.; Singh, V. K. Tungstic acid-hydrogen peroxide. A simple reagent for oxidation of cycloocta-1,5-diene preparation of (Z)cyclooct-5-ene-trans-1,2-diol and 1,6-dicarbomethoxy(Z)hex-3-ene. Synth. Commun. 1988, 18, 617–624.Search in Google Scholar

[22] Deota, P. T.; Desai, R.; Valodkar, V. B. Reaction of tungstic acid-hydrogen peroxide with endo-dicyclopentadiene: an unusual observation. J. Chem. Res. (S) 1998, 9, 562–563.Search in Google Scholar

[23] Senanayake, C. H. Applications of cis-1-amino-2-indanol in asymmetric synthesis. Aldrichim. Acta 1998, 31, 1–32.Search in Google Scholar

[24] Brewster, D.; Myers, M.; Ormerod, J.; Otter, P.; Smith, A. C. B.; Spinner, M. E.; Turner, S. Prostaglandin synthesis: design and execution. J. Chem. Soc. Perkin Trans 1973, 1, 2796–2804.Search in Google Scholar

[25] Taylor, J. E. Catalytic cis to trans conversions; dihydroxybicyclo[2.2.1]heptanes and 1,2-dihydroxyindane. Synthesis 1985, 1142–1144.10.1055/s-1985-31454Search in Google Scholar

[26] National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, approved standard, third ed. NCCLS Publication M7-A3; NCCLS: Villanova, PA, 1993.Search in Google Scholar

[27] National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal testing of yeasts, proposed standard. NCCLS Document M27-P; NCCLS: Villanova, PA, 1992.Search in Google Scholar

[28] Narasimhan, N. S.; Mali, R. S. Synthetic application of lithiation reaction; ix. A simplified synthesis of isocoumarin. Synthesis 1975, 796–797.10.1055/s-1975-23932Search in Google Scholar

Received: 2014-6-24
Accepted: 2014-9-8
Published Online: 2014-10-2
Published in Print: 2014-10-1

©2014 by De Gruyter

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Recent advances in dibenzo[b,f][1,4]oxazepine synthesis
  4. Recent trends in synthesis of five- and six-membered heterocycles using dimethyl N-cyanodithioiminocarbonate
  5. Preliminary Communication
  6. 12T061C, a new Julichrome family radical scavenger from Streptomyces species
  7. Research Articles
  8. Synthesis of pyrimido[4′,5′:2,3][1,4]thiazepino[7,6-b]quinolines, derivatives of a novel ring system
  9. Solvent-free multicomponent assembling of aldehydes, N,N′-dialkyl barbiturates and malononitrile: fast and efficient approach to pyrano[2,3-d]pyrimidines
  10. One-pot, three-component synthesis of pyranocoumarins containing an aroyl group
  11. Selective fluorescence sensor for Cu2+ with a novel triazole Schiff-base derivative with coumarin units
  12. Microwave-assisted synthesis of (E)-7-[(1-benzyl-1H-1,2,3-triazol-4-yl)methoxy]-8-(3-arylacryloyl)-4-methyl-2H-chromen-2-ones and their antimicrobial activity
  13. One-pot synthesis of 3,4-dihydro-3-hydroxyisochroman-1-one and evaluation of acetal derivatives as antibacterial and antifungal agents
  14. Copper-mediated ligand-free Ullmann reaction approach to substituted s-triazines: rationale, synthesis, and biological evaluation
https://doi.org/10.1515/hc-2014-0136
Keywords for this article
acetals; antibacterial; antifungal; 3,4-dihydro-3-hydroxyisochroman-1-one; lactol
Creative Commons
BY-NC-ND 3.0

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Recent advances in dibenzo[b,f][1,4]oxazepine synthesis
  4. Recent trends in synthesis of five- and six-membered heterocycles using dimethyl N-cyanodithioiminocarbonate
  5. Preliminary Communication
  6. 12T061C, a new Julichrome family radical scavenger from Streptomyces species
  7. Research Articles
  8. Synthesis of pyrimido[4′,5′:2,3][1,4]thiazepino[7,6-b]quinolines, derivatives of a novel ring system
  9. Solvent-free multicomponent assembling of aldehydes, N,N′-dialkyl barbiturates and malononitrile: fast and efficient approach to pyrano[2,3-d]pyrimidines
  10. One-pot, three-component synthesis of pyranocoumarins containing an aroyl group
  11. Selective fluorescence sensor for Cu2+ with a novel triazole Schiff-base derivative with coumarin units
  12. Microwave-assisted synthesis of (E)-7-[(1-benzyl-1H-1,2,3-triazol-4-yl)methoxy]-8-(3-arylacryloyl)-4-methyl-2H-chromen-2-ones and their antimicrobial activity
  13. One-pot synthesis of 3,4-dihydro-3-hydroxyisochroman-1-one and evaluation of acetal derivatives as antibacterial and antifungal agents
  14. Copper-mediated ligand-free Ullmann reaction approach to substituted s-triazines: rationale, synthesis, and biological evaluation
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 23.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/hc-2014-0136/html
Scroll to top button