The synthetic value of enzymes is being increasingly recognized. With an understanding of enzyme-catalyzed reactions and the techniques now available for the low-cost production and rational alteration of enzymes and for the design of new enzymatic activities, biocatalytic synthesis should become one of the most valuable synthetic methods. The fundamental as well as the practical issues of this rapidly growing area are described and its impact on the technology pertaining to synthesis is considered.

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New alpha-thiohemiaminals, 7alpha-phenylthio-7-epideoxynupharidin-6-ol, the diasteriomeric 7beta-phenylthiodeoxy-nupharidin-6-ol, and 3-methyl-3-methylthio-4-hydroxyquinolizidine, were prepared and reduced to the corresponding beta-tert-amino sulfides. The configuration at C-7 of the beta-tert-amino sulfides was determined by observing the direction of the solvent-induced shift of the C-7 methyl proton resonance. The configuration at C-7 of the new alpha-thiohemiaminals was established by correlations with the beta-tert-amino sulfides and confirmed, in the case of the deoxynupharidine derivatives, by circular dichroism and ascertaining the sterochemistry of deuteride incorporation upon sodium borodeuteride reduction of the alpha-thiohemiaminal. The in vitro antifungal activities of six compounds possessing the quinolizidine skeleton, including all the newly synthesized compounds as well as some previously reported ones, and amphotericin B were tested against several human pathogenic fungi. Besides amphotericin B, only the two deoxynupharidine alpha-thiohemiaminals were active, especially against Histoplasma capsulatum and Blastomyces dermatitidis. The observations indicate activity is derived from the 3-furyl group and the functionality from which alpha-thioimmonium ions can be produced.

6-and 6'-hydroxyneothiobinupharidine were isolated from Nuphar luteum from Poland. The presence of infrared Bohlmann bands, hydroxyl groups reduced by sodium borodeuteride, and the appearance of the pairs of peaks at mle 230 and 228 and 178 and 176 in the mass spectrum indicated the dual hemiaminal-amine nature of each of the two alkaloids. The 'H NMR signals at 6 4.57 given by the one isomer and at 6 4.08 given by the other demonstrated that the hemiaminal hydroxyl was located at a C-6 or C-6' position. On sodium borodeuteride reduction, singly labeled neothiobinupharidines were formed, that from the C-6 hemiaminal giving mle 179 but that from the C-6' hemiaminal giving m/e 178. The absence of the C-6 axial proton and the appearance of the C-6 equatorial proton as a singlet in the lH NMR indicated the presence of an axial deuterium at C-6 in neothiobinupharidine-6-dl. Similar evidence indicated that the deuterium atom in neothiobinupharidine-6'-dl was axial also. The CD of both hemiaminals in acid gave negative bands, the one from the C-6 hemiaminal appearing at 295 nm, and the one from the C-6' hemiaminal appearing at 279 nm.