CRYSTAL AND MOLECULAR STRUCTURE OF 14α-ACETOXY-13α-HYDROXYMULIN-11-EN-20-OIC ACID MONOHYDRATE

Abstract

The structure of this 14α-acetoxy-13α-hydroxymulin-11-en-20-oic acid monohydrate consists of a mulinane skeleton and the corresponding isopropyl, methyl, carboxyl and methyl groups at C3, C8, C5, C13, respectively, which are β-oriented, whereas the hydroxyl and acetoxy groups at C13 and C-14 are α-oriented. The cyclopentane (A), cyclohexane (B) and cycloheptene (C) rings are trans (A/B) and (B/C) cis fused, and in an envelope, chair, and twist conformation respectively. In the crystal the organic molecules are linked by the water molecules by two intermolecular OH⋅⋅⋅O hydrogen bond forming 1D-dimensional chains with graph-set notation (9).

Mulinane- and Azorellane-Type Diterpenoids: A Systematic Review of Their Biosynthesis, Chemistry, and Pharmacology

“…Natural mulinanes and azorellanes isolated from A. compacta, A. madreporica, M. crassifolium, and Laretia acaulis, together with a number of semisynthetic derivatives, were evaluated against susceptible M. tuberculosis (H37Rv) and MDR (resistant to Streptomycin, Isoniazid, Rifampin, Ethambutol, and Pyrazinamide) clinical isolate using the Microplate Blue Alamar Assay (MABA). The natural mulin-11-en-13α,20-diol (8), azorellanol (9), 13β-hydroxyazorellane (15), azorellanone (17), 17-acetoxy-13-α-hydroxyazorellane (27), semisynthetic 13α-hydroxy-mulin-11-en-20-oic-acid methyl ester (56), mulin-11,13-dien-20-oic acid methyl ester (57), and mulinenic acid methyl ester (60) were the most active against both strains (MIC = 12.5-25 µg/mL) [54,57], taking into account that a MIC of ≤64 µg/mL is considered promising for a pure product [64]. Preparation of several C-20 alkylated mulinane derivatives confirmed reports that methylation of the C-20 carboxyl group of the mulinane skeleton improves activity [59]; the most active derivatives, with MIC values between 6.25 and 25 µg/mL against the drug-sensitive and drug-resistant strains of M. tuberculosis, included 13α-hydroxy-mulin-11-en-20-oic acid n-propyl-ester (62), the isomulinic acid n-propyl ester (74), and the isomulinic acid n-butyl ester (75).…”

“…-mulin-9,12-diene (mulin-9,12-dien-7β-yl acetate)[22,57,58] 7β-acetoxy-12α,13α-dihydroxy-mulin-9-ene (mulin-12α,13α-dihydroxy-9-en-7β-yl acetate)[54,57] 7-oxo-mulin-9,12-diene (mulin-9,12-dien-7-one) 13α-hydroxy-mulin-11-en-20-oic-acid methyl ester (mulin-13α-hydroxy-11-en-20-oic acid methyl ester)Mulin-11,13-dien-20-oic acid methyl ester Mulin-20-oic acid 17-acetoxy-mulinic acid methyl ester (mulin-17-acetoxy-11,14-peroxi-12-en-20-oic acid methyl ester)Mulinenic acid methyl ester (mulin-13α,17-oxy-11-en-20-oic acid methyl ester) 13α-hydroxy-mulin-11-en-20-oic-acid ethyl ester(mulin-13α -hydroxy-11-en-20-oic acid ethyl ester)[54,59] 13α-hydroxy-mulin-11-en-20-oic-acid n-propyl ester (mulin-13α -hydroxy-11-en-20-oic acid n-propyl ester) Mulin-11,13-dien-20-oic acid ethyl ester Mulin-11,13-dien-20-oic acid n-propyl ester Mulin-11,13-dien-20-oic acid n-butyl ester Mulin-11,13-dien-20-oic acid iso-propyl ester Mulin-11,13-dien-20-oic acid iso-butyl ester Mulin-11,13-dien-20-oic acid sec-butyl ester 17-acetoxy-mulinic acid n-propyl ester (mulin-17-acetoxy-11,14-peroxi-12-en-20-oic acid n-propyl ester) 17-acetoxy-mulinic acid iso-butyl ester (mulin-17-acetoxy-11,14-peroxi-12-en-20-oic acid iso-butyl ester) 17-acetoxy-mulin-9(11),13(14)-dien-20-oic acid n-propyl ester (mulin-17-acetoxy-9(11),13(14)-dien-20-oic acid n-propyl ester) 17-acetoxy-mulin-9(11),13(14)-dien-20-oic acid iso-propyl ester (mulin-17-acetoxy-9(11),13(14)-dien-20-oic acid iso-propyl ester) 17-acetoxy-mulin-9(11),13(14)-dien-20-oic acid sec-butyl ester (mulin-17-acetoxy-9(11),13(14)-dien-20-oic acid sec-butyl ester) Isomulinic acid n-propyl ester (mulin-11,12,13,14-diepoxy-20-oic acid n-propyl ester) Isomulinic acid n-butyl ester (mulin-11,12,13,14-diepoxy-20-oic acid n-butyl ester) Isomulinic acid iso-propyl ester (mulin-11,12,13,14-diepoxy-20-oic acid iso-propyl ester) Isomulinic acid iso-butyl ester (mulin-11,12,13,14-diepoxy-20-oic acid iso-butyl ester) Isomulinic acid sec-butyl ester (mulin-11,12,13,14-diepoxy-20-oic acid sec-butyl ester) 2,13α-dihydroxymulin-11-ene (mulin-11-en-2,13α-diol) [50] Mulinic acid methyl ester (mulin-11,14-peroxi-12-en-20-oic acid methyl ester) [22] 7α,16-diacetoxy-11,13-dien-20-oic acid (mulin-7α,16-diacetoxy-11,13-dien-20-oic acid) [51] 16-acetoxymulin-11,13-dien-20-oic acid (mulin-16-acetoxy-11,13-dien-20-oic acid) 16-hydroxymulin-11,13-dien-20-oic acid methyl ester (mulin-16-hydroxy-11,13-dien-20-oic acid methyl ester) 16-acetoxymulin-11,13-dien-20-oic acid methyl ester (mulin-16-acetoxy-11,13-dien-20-oic-acid methyl ester) 7α,16-dihydroxymulin-11,13-dien-20-oic acid methyl ester (mulin-7α,16-dihydroxy-11,13-dien-20-oic acid methyl ester) 7α,16-diacetoxymulin-11,13-dien-20-oic acid methyl ester (mulin-7α,16-acetoxy-11,13-dien-20-oic acid methyl ester) 12-oxo-11α,13α-dihydroxymulin-20-oic acid (mulin-11α,13α-dihydroxy-12-oxo-20-oic acid) [58] 11-oxo-12α,13α-dihydroxymulin-20-oic acid (mulin-12α,13α-dihydroxy-11-oxo-20-oic acid)11,12-dioxo-13α-hydroxymulin-20-oic acid (mulin-13α-hydroxy-11,12-dioxo-20-oic acid) Mulin-9,12-dien-7-ol 7β-acetoxy-12,13-dihydroxymulin-9-en (mulin-12,13-dihydroxy-9-en-7β-yl acetate)14α-acetoxy-13α-hydroxymulin-11-en-20-oic acid monohydrate (mulin-14α-acetoxy-13α-hydroxy-11-en-20-oic acid monohydrate)[60] * Previously reported as natural product.…”