38 Total Synthesis of TAN-1085
Details
TAN-1085 (1) is an antibiotic of Streptomyces origin, which has attracted considerable synthetic interest due to the unique structure, a curved tetracyclic core glycosylated with a rhodinose, and important biological activities. These structual features as well as the significant biological activities led us to undertake the synthesis of this class of compounds. We report herein the first total synthesis of 1. Although initial study for the key thermal reaction with 2 occurred only the [1,7]-shift of allylic hydrogen, thereby giving enol ether 4. However, we discovered that compound 18 could be directly converted to naphthodialdehyde 19 under the Swern oxidation conditions, where the ring opening of benzocyclobutane and subsequent 6π-closure occurred at room temperature. Stereoselective pinacol cyclization by using Sml_2, followed by direct quenching of the resulting pinacolization product with benzoyl chloride exclusively gave C(5)-benzoate 21 in good yield. Glycosylation of 22 was conducted by the reaction with glycosyl donor 23 in the presence of BF_3・OEt_2, giving an 1:1 mixture of 24 and 25. Although stereochemistries of aglycon part of these were not determined, each of these was converted to the final product. One of these was identified as the natural form by comparison with authentic specimen 1. In conclusion, the first synthesis of TAN-1085 (1) was achieved. Currently we are studying the asymmetric synthesis of 1 without resort to diastereomer separation.
