Synthesis of the Spermidine Alkaloid (−)-(4R)-Dihydroisomyricoidine

✍ Scribed by Albert Horni; Anthony Linden; Manfred Hesse

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: German
• Weight: 885 KB
• Volume: 81
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19980810541

✦ Synopsis

An asymmetric synthesis of (~)-(4R)-dihydroisomyricoidine (28). a 13-membered amino lactam of type A. was performed by a diastereoselective Mic,hae/ addition between the spermidine derivative 3 and the commercially available optically active ethyl carboxylate 4, and the cyclization of the resulting co-amino acid 7 using diethyl phosphorocyanidate ((EtO),POCN), followed by a Wirtig reaction to introduce the (Z)-side chain. Some side reactions are also discussed.

Introduction.

-In 1936, the first spermidine alkaloid, containing a 13-membered ring, was isolated from the plant material of Equisetum pufustre L. [I]. Since then, more than 30 different natural products, which contain a 13-membered ring system, built up from spermidine and a fatty or a cinnamic-acid unit, have been extracted from plants [2]. Due to the non-asymmetric structure of spermidine, two constitutionally different ring systems are possible and, in fact, both are found in nature. Although the biomimetic pathway is not yet well understood, we propose, that it follows a Michael addition of spermidine to an a$-unsaturated fatty acid, followed by an intramolecular cyclization with the loss of H,O (Scheme I). Recently, we reported the enantioselective synthesis of ( -)-(2R)-dihydromyricoidine [3], a type-B alkaloid, which was isolated from Maytenus loeseneri URB. (Celastraceae) [4] and Clerodendrum myricoides VATKE (Verbenaceae) [S]. It was in our interest to synthesize the isomeric compound of dihydromyricoidine, dihydroisomyricoidine, in which a ring system of type A is present, and which has not yet been found in Nature.

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