Synthetic studies on batzelladine A, pamamycin-607, and FR901483

Abstract

Synthesis of batzelladine A 1 was proposed by the coupling reaction between β-lactam 72 and diamine 73. β-Lactam 72 was prepared from D-alanine through 8 steps. Synthesis of diamine 73 was variously attempted using regioselective epoxidation of olefin 88a-f, Wittig olefination of aldehyde 97, 99, 104a and 104b with phosphonium salt 100a-c and 103, and substitution of alkyl chain into aziridine 122 and epoxide 123 by organocuprates. Pamamycin-607 28 consists of two subunits, $C_1``-C_11``$ and $C_1-C_18$. For synthesis of $C_1-C_18$ subunits, the coupling component 142 was prepared from 1,4-butanediol using crotylboration in 7 steps. Another coupling segment 152a-c was made from D-mannitol using crotylboration and allylboration in 9 steps. Wittig olefination of 142 with 152c gave 153c, of which the internal olefin was selectively epoxidized to provide 154 and 155. Formation of tetrahydrofuran 156 was attempted under various acidic conditions. For synthesis of FR901483 58, formation of pyrrolidine ring by 5-endo cyclization of homoallylic amine 172b was executed to give 164 as model study. Wittig olefination of ketone 163 with phosphonium salt 164 afforded olefin 168. Tyrosine derivative 161 was coupled with 170b, 178b, 179 and 180 to produce 181a and 181b. Mercury(Ⅱ) ion-induced cyclization of 181a and 181b followed by hydrogenation was attempted to give a 1:1 mixture of the desired product 187a and the undesired 187b.