Sterol stereochemistry

The sterol sulfate, halistanol disulfate B (544) was isolated from a South African Pachastrella sp. The structure and stereochemistry of compound 544 were established mainly by interpretation of spectral data. Halistanol disulfate B (544) was active in the endothelin converting enzyme (ECE) assay at a micromolar concentration [451]. Three sterol trisulfates (545-547) have been isolated from the sponges Trachyopsis halichondrioides and Cymbastela coralliophila [452]. 

Most steroids are alcohols, and accordingly are named as sterols. Important examples include cholesterol, ergosterol, estradiol, stigmasterol, and other representative sterols given in Table 30-2. As you can see from their structures, most possess the same ring skeleton but vary considerably in their peripheral structural features, stereochemistry, and in the degree of ring unsaturation. 

Asymmetric epoxidation, dihydroxylation, aminohydroxylation, and aziridination reactions have been reviewed.62 The use of the Sharpless asymmetric epoxidation method for the desymmetrization of mesa compounds has been reviewed.63 The conformational flexibility of nine-membered ring allylic alcohols results in transepoxide stereochemistry from syn epoxidation using VO(acac)2-hydroperoxide systems in which the hydroxyl group still controls the facial stereoselectivity.64 The stereoselectivity of side-chain epoxidation of a series of 22-hydroxy-A23-sterols with C(19) side-chains incorporating allylic alcohols has been investigated, using m-CPBA or /-BuOOH in the presence of VO(acac)2 or Mo(CO)6-65 The erythro-threo distributions of the products were determined and the effect of substituents on the three positions of the double bond (gem to the OH or cis or trans at the remote carbon) partially rationalized by molecular modelling. 

Figure 6.10 De novo biosynthesis of isoprenoid pheromone components by bark and ambrosia beetles through the mevalonate biosynthetic pathway. The end products are hemiterpenoid and monoterpenoid pheromone products common throughout the Scolytidae and Platypodidae (Figure 6.9A). The biosynthesis is regulated by juvenile hormone III (JH III), which is a sesquiterpenoid product of the same pathway. The stereochemistry of JH III is indicated as described in Schooley and Baker (1985). Although insects do not biosynthesize sterols de novo, they do produce a variety of derivatives of isopentenyl diphosphate, geranyl diphosphate, and farnesyl diphosphate. Figure adapted from Seybold and Tittiger (2003).

The formation of a complex with membrane sterols requires penetration of the glycoside into the membrane (corresponding blocks are connected by an arrow). Owing to the ability of an aglycon to form a complex [175] the corresponding block is connected with the structural elements related to an aglycon part of the molecule. The stereochemistry of lanostane nucleus plays a major role in the formation of this complex, besides, the presence of 18(20)-lactone is also important [9, 42] (these functional relations are depicted by bold arrows). 

Fig. 14. The stereochemistry of desaturation of C>22,23 in higher plant algal and fungal sterols [9].

The most notable sterol isolated by Kobayashi from the soft coral S. glaucum was a new C27-sterol named glaucasterol (57) [62], shown to have the same structure as papakusterol isolated from deep sea gorgonians [63]. The 245, 25S stereochemistry of this sterol has been established by synthesis [64] and correlation with occelasterol... 

Synthesis of a marine sterol, depresosterol (25), illustrates the utility of the homoenolate as a multifunctional, three-carbon building block. Homo-Reformatsky reaction between an alkoxytitanium homoenolate (11 Section 1.14.5.1) and an aldehyde (19) afforded the undesired Cram product (20) in a ratio of >6 1 (Scheme 29). Inversion of the stereochemistry at the sterically hindered C-22 position was achieved through internal solvolysis by taking advantage of the terminal ester function. Stereoselective hydroxymethylation of the lactone (22) followed by introduction of the C-26 and C-27 methyl groups to (23) afforded depresosterol (25). 

Stereochemical studies on the fluorination of steroids and carbohydrates with polymer supported fluoride gave clean SN2 reactions34. The polymer supported fluoride was subjected to additional dehydration by refluxing in benzene. The stereochemistry and yields are very similar to those obtained by the fluorination of sterols with phenylfluorophosphanes35 rather than... 

Structure Voser et at., ibid. 35 2414(1952) Barnes et af.t J. Chem. Soc. 1953 571, Stereochemistry eidem, ibid. 1953, 576, Prepn from isocholesterol Bloch, Urcch, Bio-Chem. Prepn. 6, 32 (t958). Prepn by cyclization of squalener Cornforth et at, Ciba Foundation Symposium of Terpenes and Sterols 1958 119 van Tamelen et a 1. J. Am. Chem. Soc. 88 4752 (1966). Mechanism of the squalene to lanosterol conversion eidem, ibid, l04 6479, 64 0 (1982). 

Our synthetic strategy involved the conversion of stigmasterol (40) into the key intermediate 42 through 41 with the correct side-chain structure and absolute stereochemistry by methodology developed by Djerassi etal. [40], The key intermediate was then converted to the requisite sterols by employing reactions outlined in Scheme 2. 

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