Divergent Synthesis of Diastereomeric Sphingosines from a Chiral Aziridine

• Published in: Bulletin of the Korean Chemical Society Vol. 37; no. 7; pp. 1095 - 1104
• Main Authors: Kang, On-Yu, Shin, Mi-Ri, Kang, Han-Young
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag GmbH & Co. KGaA 01.07.2016; Wiley‐VCH Verlag GmbH & Co. KGaA; 대한화학회
• Subjects: Aziridine; Divergent synthesis; Ring expansion; Ring opening; Sphingosine; 화학
• ISSN: 1229-5949; 0253-2964; 1229-5949
• DOI: 10.1002/bkcs.10830

All four stereoisomers of sphingosines were synthesized starting from a single intermediate, chiral aziridine (2), which was efficiently prepared by enzymatic desymmetrization in an enatiopure form. Aziridine (2) was converted to 3, which was used for the synthesis of 4. Both the advanced key intermediates, vinylaziridines 3 and 4, were successfully converted to threo‐sphingosines 1a and 1b, respectively. Ring‐closing metathesis (RCM) using the Grubbs II catalyst was the key reaction in the synthesis. Two erythro‐sphingosines 1c and 1d were synthesized by the ring‐expansion reactions of vinylaziridines 3 and 4, followed by RCM reactions. The successful divergent synthesis confirmed that chiral vinylaziridine 2 can be used as a key intermediate for the synthesis of sphingosine‐related natural products.