Synthesis of Southern (C1'-C11') and Eastern (C8-C18) Fragments of Pamamycin-607, an Aerial Mycelium-inducing Substance of Streptomyces alboniger

Synthesis of the L‐Acid (C1–C18) Fragment of Pamamycin‐593 and De‐N‐methylpamamycin‐579

“…The total syntheses of 1 and its relatives were also achieved by Metz's,4b,4c Lee's,4d Kang's,4e and Hanquet's4f groups using a sulfone‐guided cyclization, radical cyclization, iodoetherification, and hydrogenation, respectively, for the key THF ring formation. Synthetic approaches to the L‐acid (L = large) fragments were also reported by Walkup's,5a Perlmutter's (oxymercuration),5b Bloch's (Michael cyclization),5c Solladié's,5d Hanquet's (hydrogenation),4f Nagumo's (phenonium ion cyclization),5e and our groups (iodoetherification) 6. Continuing our synthetic work of pamamycins,6,7 we began the synthesis of these new compounds 2 and 3 for further biological studies.…”

“…Synthetic approaches to the L‐acid (L = large) fragments were also reported by Walkup's,5a Perlmutter's (oxymercuration),5b Bloch's (Michael cyclization),5c Solladié's,5d Hanquet's (hydrogenation),4f Nagumo's (phenonium ion cyclization),5e and our groups (iodoetherification) 6. Continuing our synthetic work of pamamycins,6,7 we began the synthesis of these new compounds 2 and 3 for further biological studies. Here we describe an efficient and convergent synthesis of the L‐acid fragment 4 .…”

“…In the previous paper, we prepared the C1–C18 portion of the L‐acid (Scheme ) 6. A Julia coupling of sulfone 6 , derived from 5 , with chiral aldehyde 7 afforded olefin 8 .…”

“…A Julia coupling of sulfone 6 , derived from 5 , with chiral aldehyde 7 afforded olefin 8 . Cis ‐selective iodoetherification followed by deiodination gave the C8–C18 fragment 9 6. However, the yields were low in the reductive desulfonylation and deiodination steps.…”

“…As shown in Scheme , our synthesis of the L‐acid 4 began with the known aldehyde 5 , which was our common starting material for the synthetic studies of polynactin and the pamamycin series 6,9. Treatment of 5 with the Ohira–Bestmann reagent10 afforded alkyne 10 (C1–C7 fragment) in 91 % yield.…”