C-24 stereochemistry of marine Sterols: (22E)-24-Ethyl-24-methylcholesta-5,22-dien-3b-oβl and 24-Ethyl-24-methylcholest-5-en-3β-ol

Abstract

As configurações dos carbonos C-24 nos compostos (22E)-24-etil-24-metilcolesta-5,22-dien-3b-ol (1) e 24-etil-24-metilcolest-5-en-3b-ol (2), isolados da esponja do caribe colombiano Topsentia ophiraphidites foram determinadas como R e S, respectivamente, com base na comparação dos seus dados de RMN com aqueles de amostras de configurações já definidas 24R e 24S, as quais foram sintetizadas em rotas envolvendo ortoésteres provenientes do rearranjo de Claisen de álcoois D 23-22 alílicos. Este é primeiro estudo de síntese, em que o rearranjo de Claisen é utilizado para introduzir um centro quaternário em C-24, de maneira estereoespecífica e com rendimento aceitável. Análises por difração de raio X de 1 confirmaram essas atribuições estereoquímicas.The C-24 configurations of (22E)-24-ethyl-24-methylcholesta-5,22-dien-3b-ol (1) and 24-ethyl-24-methylcholest-5-en-3b-ol (2), isolated from the Colombian Caribbean sponge Topsentia ophiraphidites, were determined to be R and S, respectively, by comparing their NMR data with those of stereodefined (24R)-and (24S)-samples that were synthesized in routes involving the orthoester Claisen rearrangement of D 23 -22-allylic alcohols. This is the first synthetic study where the Claisen rearrangement is used to introduce a C-24 quaternary center in a stereospecific manner with acceptable yield. X-ray analysis of 1 confirmed these stereochemical assignments.

Neo-5,22E-Cholestadienol Derivatives from Buthus martensii Karsch and Targeted Bactericidal Action Mechanisms

“…From the above, compound 1 was confirmed as a novel cholesterolenone structure [7,8] based on the analysis of spectral data of 1 and the comparison with the literature. Compound 1 was then named as (−) 22 E , 3-oxocholesta-4, 22 (23)-dien-25-ol according to reported compound in the literature (+) (22 E , 24α)-24-Ethyl-3-oxocholesta-4, 22 (23)-dien-25-ol [9], which the latter for known compound has one ethyl group former on C-24 (for details in Figure 3).…”

“…Since the optical rotation [α]D25 −22.7° of compound 1 exhibited a negative Cotton effect at 223.5 nm for the determination of its CD spectra, and it was inferred to be a levorotatory configuration compound of enantiomers contrasted with known compound (+)7 S ,8 S ,9 R ,13 R ,14 S ,17 R ,24 S ,20 R (22 E ,24α)-24-Ethyl-3-oxocholesta-4, 22(23)-dien-25-ol [9]. Accordingly, the structure of compound 1 was elucidated as a new cholestadienol shown and named as (−) 7 S , 8 S , 9 R , 13 R , 14 S , 17 R , 20 S (22 E )-3-oxocholesta-4, 22(23)-dien-25-ol in Figure 1.…”

C-24 Stereochemistry of Marine Sterols: (22E)-25,28-Dimethyl-stigmasta-5,22,28-trien-3β-ol and 25,28-Dimethylstigmasta-5,28-dien-3β-ol

“…We previously reported the isolation of a number of multiple alkylated sterols including a new C 31 -sterol, ophirasterol [(22E)-24-(1-buten-2-yl)cholesta-5,22-dien-3-ol], from the Colombian Caribbean sponge, Topsentia ophiraphidites [1]. Among these sterols, the C-24 configurations of ophirasterol [1], 24-ethyl-24methyl-22-dehydrocholesterol [2], 24-ethyl-24-methylcholesterol [2] and 24-isopropenyl-22-dehydrocholesterol [3] were established through the synthesis of stereochemically defined (24S)-and (24R)epimers of these sterols. However, the C-24 configurations of the tbutyl containing sterols, (22E)-25,28-dimethylstigmasta-5,22,28trien-3-ol (1a or 1b, compound with unknown stereochemistry is designated as 1 hereafter) and 25,28-dimethylstigmasta-5,28-dien-3-ol (2a or 2b, compound with unknown stereochemistry is designated as 2 hereafter) have remained to be established ( Figure 1).…”

“…To elucidate the C-24 configurations of 1 and 2 we adopted the same strategy as employed in our previous studies [1][2][3]. This involves the synthesis of stereochemically defined both C-24 epimers and comparison of the NMR spectroscopic data with those of natural sterols.…”

“…Exposure of the (22R)-allylic alcohol 7a to conditions of orthoester Claisen rearrangement (triethyl orthopropionate in refluxing xylene containing propionic acid) gave the rearranged ester 11a in a moderate yield as a C-28 diastereomeric mixture (this was confirmed at the stage of 12a and the subsequent transformation yielded 13a as a single compound). The configuration at C-24 of 11a was assigned as R from the well-established conformation in the transition state of the orthoester Claisen rearrangement of steroidal (23E)-23-en-22-ols [1][2][3]9,11]. Reduction of the ester 11a gave the primary alcohol 12a, which upon dehydration afforded the exomethylene 13a as a stereochemically homogenous compound.…”