An Organotrifluoroborate-Based Convergent Total Synthesis of the Potent Cancer Cell Growth Inhibitory Depsipeptides Kitastatin and Respirantin

• Published in: Organic letters Vol. 16; no. 9; pp. 2322 - 2325
• Main Authors: Beveridge, Ramsay E., Batey, Robert A.
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 02.05.2014; Amer Chemical Soc
• Subjects: Antimycin A - analogs & derivatives; Antimycin A - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Borates - chemistry; Chemistry; Chemistry, Organic; Depsipeptides - chemical synthesis; Depsipeptides - chemistry; Depsipeptides - pharmacology; Hydrocarbons, Fluorinated - chemistry; Leucine - analogs & derivatives; Leucine - chemistry; Molecular Structure; Physical Sciences; Science & Technology; ALCOHOLS; ANTI CROTYLATION; LEWIS-ACID; ALLYLATION; ANTINEOPLASTIC AGENTS; CARBOXYLIC ESTERS; ALDEHYDES; STEREOSELECTIVE-SYNTHESIS; HIGHLY DIASTEREOSELECTIVE SYN; DERIVATIVES
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol500484f

The total syntheses of the highly cytotoxic neo-antimycin macrocyclic depsipeptide natural products kitastatin and respirantin have been accomplished in a convergent manner using MNBA promoted esterifications and an efficient C- and N-terminus bis-deprotection/HATU promoted macrolactamization. The first examples of using a prenyltrifluoroborate reagent in additions to carbonyl groups are disclosed including a diastereoselective multigram scale montmorillonite K10 catalyzed prenylation of N-Boc-l-leucinal to install the structurally unique gem-dimethyl-β-keto-ester fragment.