Absolute stereochemistry, steroids

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

There are three classes of cyclic peroxides that were found in marine sponges steroidal peroxides, norsesterterpene and norditerpene peroxides, and polykide peroxides many of them were isolated and their relative and absolute stereochemistry was determined. Most of them (even as crude extracts) show exceptional antimicrobial and antifungal propoperties (cf. Section 8.10.3). For example, the norsesterterpene 1,2-dioxides mycaperoxides A and B 222 and 223 (Scheme 63) showed significant cytotoxicity and in vitro antiviral activity. 

Aphidicolin is a diterpenoid metabolite of Cephalosporium aphidicola and Phoma betae. The strueture of aphidieolin (5.126) was established in 1972 through a eombination of ehemieal, spectroseopie and X-ray crystallographic studies. Unlike the ent-kaurene and gibberellin metabolites of G. fujikuroi, aphidicolin possesses an absolute stereochemistry that is steroid-like . It has attracted considerable interest as a specific inhibitor of DNA polymerase a and as a potential anti-viral and anti-tumour agent. 

Evidence for the relative and absolute stereochemistry, which was reported in 1965, was based on a more detailed analysis of the NMR spectra and on the signs of the circular dichroism curves of various ketones when compared to steroid models. The stereochemistry was finally confirmed by X-ray crystallography. 

In addition to the regioselective oxidation of the hydroxy groups in virtually every position, a discrimination of the absolute stereochemistry can be achieved by various a- or (3-selective HSDHs. Thus, the stereoinversion of various steroids was achieved by successive oxidation at position 3 with 3a-HSDH and subsequent reduction with 30-HSDH (Fig. 16.2-20)1841. Hydroxy functions in other positions were not modified, and the products at the end of the sequence were essentially pure. Because of the low solubility of the reactants, biphasic systems with ethyl (butyl) acetate as organic solvents were used as reaction media. 

The 9,11-seco steroid (68) was formed with the desired natural (135,145) absolute stereochemistry. Conversion of a racemic sample of (68) into racemic steroidal equilenin (69) was used to demonstrate the potential of this methodology for the total synthesis of enantiomerically pure steroidal material of natural configuration, although an enantiomerically pure synthesis was not performed [46]. 

First, it was necessary to establish the absolute stereochemistry of the steroid nucleus. 

The establishment of the absolute stereochemistry of the side chain of the steroid nucleus, coupled with the knowledge of the relative stereochemistry of the remainder of the steroid system and the wealth of information derived from decades of the study of the chemistry of steroids was then used to define the absolute stereochemistry of (15,25)-(-)-2-carboxy-2-methylcyclohexane acetic add. Although it is... 

The structure and stereochemistry of chiloscyphone (74) have been determined and o.r.d. and c.d. spectra are consistent with a non-steroidal conformation. " From Taiwania cryptomerioides, three new muurolane-type sesquiterpenoids have been isolated" viz., (75), (76), and (77). In accordance with the absolute... 

With the absolute configuration of the atisine and Garrya alkaloids established, it is interesting to note that these compounds join the ranks of terpenes with antipodal stereochemistry of the A/B ring fusion as compared with that of the steroids, e.g., andrographolide, atisirene, cafestol. 

Similar NMR studies of MTPA esters showed that there was a correlation between the shape of the signals due to the CH2OH (C-26) group in the R) and (5)-MTPA esters and the absolute configuration at C-25. This new approach (i.e., comparison of the chemical shifts of the methylene protons at C-26 in the spectra of the R) and (S)-MTPA esters) has the advantage of avoiding the use of europium salts and has been widely used by researchers interested in the stereochemistry of steroid side chains. ... 

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