Natural products Neplanocin

In kinetic resolutions (Scheme 3.2-3.5) it is often the case that one of the products is required, while the other is not and must be discarded or recycled (e.g. racemised). Such operations can be wasteful or expensive. On the other hand, the biotransformation of wcso-compounds or prochiral compounds allows for the possibility of preparing an optically pure compound in quantitative yield. In Scheme 3.7, two examples of the use of meso-compounds are described. The diester (11) is made up of a complex dicarboxylic acid unit derivatised as the dimethyl ester. Pig liver esterase catalyses the hydrolysis of one of the ester groups to give the acid (12) (95% e.e.) in 96% yield. This compound is an excellent precursor of the natural product neplanocin. Note that the acid (12) is not a substrate for pie, and thus the reaction stops at the half-way stage. The compound (13), like (11), possesses a plane of symmetry. Hydrolysis catalysed by porcine pancreatic lipase (ppl) affords the alcohol (14) (>98% e.e.) in quantitative yield. The latter compound has been used to make fluorocarbocyclic adenosine (C -adenosine), a stable analogue of the naturally occurring nucleoside adenosine. 

During the past few years, acylnitroso Diels-Alder cycloadditions have been used as the key step in several natural product total syntheses. Retey et al.40 have used the adduct from cyclopentadiene and the acylnitroso compound derived from 3,5-dinitrobenzoic acid35 to synthesize the antitumor compound neplanocin A (16) (Scheme 3-XI). 

The endo cycloadducts resulting from the cycloaddition of optically active 3-(2-pyridylsulfinyl)acrylates and simple dienes such as cyclopentadiene and furan have been utilized successfully in the asymmetric synthesis of several natural products [166-170]. For example, cycloadduct (197), synthesized as a single diastereoisomer from the reaction of (5)-3-(2-pyridylsulfinyl)acrylate with cyclopentadiene, was converted to the lactone (198) [166], a key intermediate in the synthesis of the carbocyclic nucleosides (-)-aristeromycin (199) and (-)-neplanocin A (200) (Scheme 5.65) [167]. 

Naturally occurring (l S, 25, 3i )-4-hydroxymethylcyclopent-4-ene-l,2,3--triol (950) plays a central role in the ability of a non-aristeromycin producing mutant strain of Streptomyces citricolor to support production of both aristeromycin and neplanocin. Swem oxidation of readily available 13 from L-tartaric acid provides the aldehyde 943 which, when treated with an excess of propargyl zinc bromide, leads to a 2.3 1 diastereomeric mixture of acetylenic alcohols 944. Silylation of the hydroxyl group with TBSOTf and subsequent saponification of the ester group yields the carboxylic acid 945 in 74% overall yield from 13. Interestingly, Dess-Martin oxidation of 943 provides the allenic ketone 946, which is unstable to base and cannot be used in the subsequent radical cyclizations. 

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