Modular synthesis of polyene side chain analogues of the potent macrolide antibiotic etnangien by a flexible coupling strategy based on hetero-bis-metallated alkenes

Abstract

An efficient procedure for the concise synthesis of hetero-bis-metallated alkenes as useful building blocks for the modular access to highly elaborate polyenes and stabilized analogues is reported. By applying these bifunctional olefins in convergent Stille/Suzuki-Miyaura couplings, novel, carefully selected side chain analogues of the potent RNA polymerase inhibitor etnangien were synthesized by a modular late stage coupling strategy and evaluated for antibacterial and antiproliferative activities.

A Short and Efficient Approach for the Total Synthesis of (S)‐Zearalenone and (R)‐De‐O‐methyllasiodiplodin by Using Stille and RCM Protocols

“…IR (neat): ν max = 3427, 2933,2857,1728,1612,1279,1160,966,855 (d, J = 6.5 Hz, 2 H), 3.83 (s, 3 H), 6.30 (d, J = 2.4 Hz, 1 H), 6.47 (d, J = 2.4 Hz, 1 H) ppm. 13 C NMR (100 MHz, CDCl 3 ): δ = 20. 1, 21.1, 24.1, 24.7, 27.2, 30.8, 31.0, 33.6, 55.2, 75.0, 98.8, 105.1, 110.5, 148.5, 163.7, 165.6, 171.9…”

“…Purification of the crude residue by silica gel column chromatography (EtOAc/PE, 10:90) to afforded saturated product 32 (17.9 mg, 90 %) as a colorless oil; R f = 0.5 (EtOAc/ PE, 10:90). 2854,1644,1612,1416,1253,1208,1157,1040,813 13 C NMR (100 MHz, CDCl 3 ): δ = 20. 1, 21.1, 24.1, 24.7, 27.2, 30.8, 31.0, 33.6, 55.2, 75.0, 98.8, 105.1, 110.5, 148.5, 163.7, 165.6, 171.9 (R)-12,14-Dihydroxy-3-methyl-3,4,5,6,7,8,9,10-…”

“…Accordingly, stannane 11 was prepared from commercially available 5-hexyn-1-ol (12). After screening a number of reports in the literature, we found the Menche protocol [13] was the most suitable to produce the required trans-vinyl stannane 11 in high yield with excellent selectivity. The Stille cross-coupling reaction of triflate 10 and stannane 11 was examined as a method to construct the C-1′-C-2′ styryl double bond of 2 (Scheme 3).…”

“…mg, 82 %) as a yellow oil; R f = 0.5 (EtOAc/PE, 10:90). 12.6, 18.8 Hz, 1 H), 2 H), 6.27 (d, J = 2.7 Hz, 1 H), 6.33 (d, J = 2.7 Hz, 1 H), 11.9 (s, 1 H) ppm 13. IR (neat): ν max = 3446, 2929, 2855, 1646, 1579, 1255, 1158, 1047, 931 cm -1 .…”

Synthesis of the all-syn C35–C39 stereopentad of etnangien by the γ-hydroxybutenolide approach

“…3 The low mammalian cell cytotoxicity of etnangien has prompted a multi-faceted scientific investigation of etnangien's potential as a therapeutic agent. 1,2,[4][5][6][7][8][9] The total synthesis of etnangien was accomplished by Menche in 2009. 6 One of the biggest challenges in the synthesis of etnangien is the construction of the stereochemically-rich polypropionate fragment of the macrocyclic moiety.…”