7-Lactones, hydrolysis

The other isomer (in this case 11) may be recycled by equilibration at room temperature. In principle this allows transformation of the whole synthetic material into either (-i-)-hamatine or (—)-ancistrocladine36,42, without the hydrolysis-lactonization cycle that is necessary for the lactones. 

An aldopentose (A) of the D-configuration on oxidation with concentrated nitric acid gives a 2,3,4-trihydroxypentanedioic acid (a trihydroxyglutaric acid) (B) which is optically inactive. (A) on addition of HCN, hydrolysis, lactonization, and reduction gives two stereoiso-meric aldohexoses (C) and (D). (D) on oxidation affords a 2,3,4,5-tetrahydroxy-hexanedioic acid (a saccharic acid) (E) which is optically inactive. Give structures of compounds (A)-(E). 

The use of sodium amalgam originates with E. Fischer. The method was a cornerstone of his aldose homologation (cyanohydrin formation, hydrolysis, lactone formation and reduction) which was so important to the development of carbohydrate chemistry. Although the yields obtained by Fischer were moderate ca. 20-50%), more recent work by Sperber et al. has resulted in significant improvements. In particular, they discovered that control of the pH of the reaction mixture was very important. At pH 3-3.5, yields in the range 52-82% were obtained with a variety of aldonolactones. As an example, the preparation of arabinose is shown in equation (4). If the pH was allowed to rise, yields were lower due to overreduction. Methyl esters of aldonic acids could also be used as substrates. 

The selective cleavage of a cyclopropane ring has also been used in a stereo-controlled total synthesis of the antitumor lactone vernolepin (10). A key step involved reaction of 4 with sodium p-methoxythiophenoxide, which was used rather than sodium thiophenoxide because the corresponding sulfoxide is less prone to i yw-elimination than a phenyl sulfoxide in the next step, 5 6. Remaining steps involved epoxidation and reduction to the diol (9). Conversion of 9 to 10 included hydrolysis, lactonization, and methylenation, accomplished in 227 yield. See structure on page 422. 

Scheme 13.6 Domino hydrolysis/lactonization/esterification reaction of the TCRA product.

Enantiomerically pure epoxide 58 was available from o-norvaline via the same route to epoxides as in our viriditoxin synthesis. Reaction of epoxide 58 with the lithium anion of OBO-sulfone 57 produced lactone in 60% overall yield after hydrolysis, lactonization, and elimination. We were pleased to discover that this reaction allowed for use of 1.3 equivalents of 57, whereas three equivalents of Ghosez s reagent were often used in related transformations. Although we have not examined the reactions of the viriditoxin or pig-mentosin A epoxides with this reagent, we hypothesize that our modified reagent 57 would allow for a unified a,(3-unsaturated lactone synthesis and thus access to a variety of derivatives of binaphthopyranones. 

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