Total synthesis of 1-156,602, a novel cyclic hexadepsipeptide antibiotic

Total synthesis of (+)-A83586C, (+)-kettapeptin and (+)-azinothricin: powerful new inhibitors of β-catenin/TCF4- and E2F-mediated gene transcription

“…9 Such a problem might arise if an alternative union of a fully elaborated cyclodepsipeptide amine hydrochloride salt and the activated ester 3 was purveyed. Although activation of the carboxyl in 1 might potentially result in a b-lactone, this too could potentially macrocyclise in the desired way over time and, given this possibility, we elected to pursue this approach with vigour, to see what would eventually come as a result.…”

“…24,25 Scheme 9 Our tandem asymmetric electrophilic hydrazinationnucleophilic cyclisation strategy for building up enantiopure piperazic acid and its application in the synthesis of the northern dipeptide 6. 9,29,30 overall yield of pure 75 from 71 was 68% without resort to chromatography and even today, 18 years after its development, 30a,b this remains the premier method for constructing this particular chiral a-hydrazino acid.…”

“…9,33 They prepared compound 78 from 76 by the pathway shown in Scheme 9 which exploited optically pure (3R)-N(1)-Z-piperazic acid to secure 6. In their synthesis, 9,33 however, optically pure (3R)-N(1)-Z-Piz was obtained using Hassall's rather low yielding procedure of ephedrine-induced optical resolution of (AE)-N(1)-Z-piperazic acid, 34 which itself had been prepared via a high-yielding Diels-Alder reaction between methyl 2,4-pentadienoate and DBAD in CCl 4 at reflux. 33 Our highly efficient tandem asymmetric hydrazination pathway to 75 and 76 thus greatly improved the prior art for obtaining 6 which utilised Carpino's Fmoc-amino acid chloride biphasic coupling technology 35 to connect the fragments 80 and 77 together.…”

Total Synthesis of 4-Epi-A83586C. Epimerisation in a Macrolactamisation Mediated by BOP and DMAP

“…Compound 14 was then converted into 15 in a further four steps and this condensed with known acid chloride 16 1 using the AgCN coupling method of Durette et al 7 The Fmoc 11 deprotection and amidation steps delivered hexapeptide 17 in a combined yield of 78%. The next phase of the synthesis was Troc to Z interconversion, 1 followed by acidolysis, to furnish 18.…”

Conformation of Isobutyl, 2,2-Dibromoethyl, and 2-Methoxypropyl Side Chains on Cyclohexane and Tetrahydropyran Ring Systems

“…We infer this to be the one depicted, since force‐field calculations for compound 4 predicted a 89% preference for conformation 4a 8. Nature uses this type of conformational preorganization of side chains in certain acid components of antibiotics such as L‐156,60211 or polyoxypeptin,12 whereby a hydrophobic part of the pharmacophore is held in a distinct shape.…”