The total synthesis of borrelidin has been achieved. The best feature of our synthetic route is macrocyclization at C11-C12 for the construction of an 18-membered ring after esterification between two segments. A detailed examination of the macrocyclization led us to the samarium(II) iodide-mediated intramolecular Reformatsky-type reaction as the most efficient synthetic approach. The two key segments were synthesized through regioselective methylation, directed hydrogenation, stereoselective Reformatsky-type reaction, and MgBr2.Et2O-mediated chelation-controlled allylation.

The total synthesis of (À)-amidepsine B, a potent diacylglycerol acyltransferase inhibitor, has been achieved. This synthetic study resulted in the revision of the previously assigned stereostructure of the natural amidepsine B and determined the absolute configuration. Keywords: absolute configuration; (À)-amidepsine B; total synthesis INTRODUCTION Amidepsines A-E were isolated from the culture broth of fungal strains FO-2942 and FO-5969 and found to be inhibitors of diacylglycerol acyltransferase (DGAT), 1-3 which is exclusively involved in triacylglycerol formation. Excessive accumulation of triacylglycerol can cause fatty liver, obesity and hypertriglyceridemia, which leads to serious diseases, such as atherosclerosis, diabetes and metabolic disorders. Therefore, DGAT inhibitors have the potential to become drugs. Spectroscopic analyses of the amidepsines elucidated depsipeptide structures consisting of three 4,6-dihydroxy-2-methylbenzoic acid derivatives and an amino acid (except for amidepsine D), as shown in Figure 1. The DGAT inhibitory activity of the amidepsines was tested by a cellular assay using Raji cells, and the results showed that amidepsine B (1) was the most potent inhibitor. Amidepsine B (1) was previously determined to be a mixture of stereoisomers at its single chiral center, the alanine alpha carbon. A 3:2 mixture of L-and D-alanines was revealed by acid hydrolysis followed by HPLC analyses using a chiral column (Amidepsines A and C were also reported as a 3:2 mixture of L-and D-amino acids 2 ). Herein, the total synthesis of amidepsine B and a revision of its absolute configuration will be described.

Antibiotics U 1200Total Synthesis of Amidepsine B (I) and Revision of Its Absolute Configuration. -(NAGAMITSU, T.; MARUMOTO, K.; NAGAYASU, A.; FUKUDA, T.; ARIMA, S.; UCHIDA, R.; OHSHIRO, T.; HARIGAYA, Y.; TOMODA, H.; OMURA*, S.; J. Antibiot. 62 (2009) 2, 69-74; Kitasato Inst. Life Sci., Kitasato Univ., Minato, Tokyo 108, Japan; Eng.) -H. Toeppel 28-189