Side Chain Elaboration

An effective 10-step procedure leading to a25-OH side chain in 42% yield from the Ci9 steroid aldosterone has been accomplished [scheme The addition 

From the C21 steroid, pregnenolone, many excellent synthetic schemes to hydroxylated side chain derivatives have been developed. Direct condensation of the 

Another creative scheme which originates from pregnenolone [scheme (6)] utilizes vinyl magnesium bromide as the initial reactant and yields the corresponding 

By far the most widely used starting material for side chain elaboration schemes has been the C-22 aldehyde. This compound, readily obtained from the ozonolysis of sigmasterol i-ether or the 4-phenyl-l, 2,4-triazoline-3,5-dione (PTAD)-diene adduct of ergosterol has been modified in a number of ways. 

Reduction to the alcohol, tosylation and conversion to the C-22 iodo derivative provides the substrate for reaction with a-(dimethyl allyl) nickel bromide. This coupling reaction gives the desmosterol side chain directly [scheme (7)]  

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Folate analogues continue to have importance in chemotherapy, especially heterocyclic analogues other than pteridines which are covered in Chapters 10.15-10.17 and 10.19. 1,3-Dimethyllumazine analogues of folates for use as model compounds have been prepared by side-chain elaboration of 6-bromomethyl-l,3-dimethyllumazine (Scheme 34) <1996JHC341>. More notable in this work, however, was the synthesis of the bromomethyl precursor itself in addition to routine bromination of the 6-methyllumazine 175 prepared by condensation of dihydroxyacetone with 5,6-diamino-l,3-dimethyluracil, a cycloaddition reaction between trimethylsilyl enol ethers and the pyrimidyl bisimine 177, via cycloadducts such as 176, afforded substituted pteridines in moderate to good yields. 

Methylquinazolin-4(3i/)-one is converted into the dianion 1 using uncomplexed butyl-lithium. Subsequent condensations of 1 with alkyl halides, ketones and aldehydes result in selective modification of the original methyl group to form derivatives 2, This reaction represents a direct, general method for side-chain elaboration of 2-alkylquinazolin-4(3//)-ones. ... 

The vinyltin moiety can form part of a diene system and undergo coupling with a dienyl iodide to form a tetraene [23] (Scheme 4-3). Crisp and Glink [24] have carried out a number of couplings directed towards -amino acid side-chain elaboration steps and observed the occurrence of ipso-substitution as a side reaction. 

The africanane sesquiterpenes have an interesting rearranged guaiane-type carbon skeleton, which can be obtained from (/ )-pulegone, ring contraction, side chain elaboration, and RCM (Scheme 24) [59]. 

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