157733-17-0Relevant articles and documents
Total Synthesis of Myxovirescins, 1. Strategy and Construction of the "Southeastern" Part
Seebach, Dieter,Maestro, Miguel A.,Sefkow, Michael,Adam, Geo,Hintermann, Samuel,Neidlein, Axel
, p. 701 - 718 (2007/10/02)
In this and the following two papers the synthesis of myxovirescins A1, A2 and M2, 28-membered macrocyclic lactam-lactones with antibiotic activity, is described.A retrosynthetic analysis of the myxovirescin family of ca. 30 target molecules leads to a strategy which could be applied to approximately half of them by slight variations of the building blocks used (Schemes 1-3 and following paper).The southeastern part of the molecule, containing the atoms O(1)-C(14) of myxovirescins A and M is described in this first paper (Scheme 3).The assembly is achieved by using the following appropriately protected units: (S)-2-hydroxy-pentanoic acid, (dithian-2-ylmethyl)-amine (Scheme 4), the triflate of (S,R)-2,2-dimethyl-5-vinyl-dioxolan-4-ylmethanol, (E)-3-bromo-2-buten-1-ol, and (E)-2-bromo-2-buten-1,4-diol (Scheme 5), the starting materials for these being malic acid, aminoacetaldehyde, ribose, crotyl alcohol and butyne-1,4-diol.The building blocks are put together by using the following key steps: Kolbe electrolysis, amide formation, lithiodithiane alkylation, and Suzuki coupling (Schemes 6 and 8).The only newly created chirality center is generated stereoselectively by a Li-selectride reduction/Mitsunobu inversion (Table 1, Scheme 7).The termini of the O(1)-C(14) fragment (2 in Scheme 8) carry a (protected) hydroxy acid and an aldehyde group for the Julia coupling and lactonization, respectively, in the final steps of the synthesis.All intermediates are fully characterized.The X-ray crystal structures of two compounds prepared for incorporation as N(4)-C(11) and as C(12)-C(14) of the target molecules are also described (Figures 1 and 2). - Key Words: Myxovirescins / Myxococcus virescens Mx v48 / Suzuki coupling / Macrolides / Lactones / Lactams / 1,3-Dioxolanes / 1,3-Dithianes / Antibiotics
