Pyrrolidinol alkaloid

The total synthesis of pyrrolidinol alkaloid, (+)-preussin was achieved in five efficient transformations from commercially available fert-Boc-(S)-phenylalanine in the laboratory of S.M. Hecht. The key step involved the Hg "-mediated 5-endo-dig cyclization of ynone substrate affording the desired pyrrolidinone which, in two more steps, was converted into the natural product. 

The reactions depicted in Scheme 39 were already conducted in view of a potential use in the synthesis of pyrrolidinols and piperidinols. The structural feature of a 2-arylmethyl-3-hydroxysubstitution is not only found in preussin but also in anisomycin (152) [87] or in the piperidine alkaloid FR 901483 (153) [88] (Fig. 5). 

Generally, the use of a catalyst containing a -hydroxy amine moiety, for example, cinchona and ephedra alkaloids or 4-(4-aminophenylmethyl)-l-ethyl-2-pyrrolidinol, gives addition products with higher optical purity or enantiomeric excess values (up to 88%). The use of polar solvents, concentrated reaction solutions and the presence of tetrabutylammonium salts can substantially lower the optical purity of the products88. 

The total synthesis of (— )-nummularine-F (163), a 4(14)-amphibine-F-type cyclopeptide alkaloid, from D-serine was accomplished in 25 steps and an overall yield of 0.48%. This approach includes a stereoselective synthesis of a cw-2-(hydroxymethyl)-3-pyrrolidinol derivative, the inversion of the cjs-3-hydroxyl function to the desired... 

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