Asymmetric synthesis of the N-terminal component of microginin: (2S,3R)-3-amino-2-hydroxydecanoic acid, its (2R,3R)-epimer and (3R)-3-aminodecanoic acid

✍ Scribed by Mark E Bunnage; Anthony J Burke; Stephen G Davies; Christopher J Goodwin

• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 714 KB
• Volume: 6
• Category: Article
• ISSN: 0957-4166
• DOI: 10.1016/0957-4166(94)00372-i

✦ Synopsis

3-Amino-2-hydroxydecanoic acid (AHDA) is a novel amino acid which has been suggested as the Nterminal component of the recently isolated angiotensin-converting "enzyme inhibitor microginin. The naturally occurring amino acid was found to possess syn relative stereochemistry and (2S,3R) absolute stereochemistry when the reported IH and 13C nmr spectroscopic data and the CD data were compared to the spectroscopic data for synthetic (2R,3R)-and (2S,3R)-AHDA. These studies complete the stereochemical assignment of microginin.

Microginin 1, a linear pentapeptide, has recently been isolated from the freshwater blue-green alga Microcystis aeruginosa, l It was found to possess angiotensin-converting enzyme (ACE) inhibitory properties, which is of considerable medical interest since ACE inhibitors have been developed as antihypertensive agents. 2 A number of techniques, principally 2D nmr spectroscopy and chemical degradation, were employed to elucidate the partial structure of 1. The degradative studies conducted upon this compound provided a novel 3-amino-2hydroxydecanoic acid (AHDA) which was considered to be the N-terminal moiety. The structure of this A/IDA was indicated by the 1H and 13C nmr spectra, and by a FAB mass spectrum. On the basis of a Cotton effect in the CD spectrum, it was further suggested that the ~-stereogenic centre in this acid was of the R configuration, however, this has to be regarded as tentative, especially since there is a 13-stereogenic centre of undefined stereochemistry present. 1 In a preliminary communication we have recently reported the completion of the stereochemical assignment of microginin, 3 through the comparison of spectroscopic data for the naturally