Convergent Total Synthesis of Paecilomycin B and 6'- epi-Paecilomycin B by a Barbier-Type Reaction Using 2,4,6-Triisopropylphenyllithium.

The convergent total synthesis of the natural product paecilomycin B and its 6'-epimer was investigated. The aryl- C-glycoside skeleton was constructed by an intramolecular Barbier-type reaction using 2,4,6-triisopropylphenyllithium and subsequent deoxygenation of the resulting anomeric hydroxy group. Starting from aryl iodide 24, the addition reaction afforded the thermodynamically stable C-ß macrocyclic adduct 41a in 29% yield and the C-α adduct 41b in 1% yield. Meanwhile, aryl iodide 43 (6'-epimer of 24) gave only the C-α adduct 44 in 76% yield. The stereoselectivities of these nucleophilic addition reactions are also discussed.

Total Synthesis of Paecilomycin B.

Starting from the glucose-derived δ-lactone and the functionalized aryl bromide, the first total synthesis of naturally occurring paecilomycin B was achieved via functionalized aryl-ß-C-glycoside synthesis using 2,4,6-triisopropylphenyllithium under Barbier-type reaction conditions and ring-closing metathesis as the key steps.

Novel Indole-N-glucoside, TA-1887 As a Sodium Glucose Cotransporter 2 Inhibitor for Treatment of Type 2 Diabetes.

Inhibition of the renal sodium glucose cotransporter (SGLT) increases urinary glucose excretion (UGE) and thus reduces blood glucose levels during hyperglycemia. To explore the potential of new antihyperglycemic agents, we synthesized and determined the human SGLT2 (hSGLT2) inhibitory potential of novel substituted 3-benzylindole-N-glucosides 6. Optimization of 6 resulted in the discovery of 3-(4-cyclopropylbenzyl)-4-fluoroindole-N-glucoside 6a-4 (TA-1887), a highly potent and selective hSGLT2 inhibitor, with pronounced antihyperglycemic effects in high-fat diet-fed KK (HF-KK) mice. Our results suggest the potential of indole-N-glucosides as novel antihyperglycemic agents through inhibition of renal SGLT2.