A Regio- and stereocontrolled total synthesis of (-)-indolactam-V

Structural Diversification of Lyngbyatoxin A by Host‐Dependent Heterologous Expression of the tleABC Biosynthetic Gene Cluster

“…Surprisingly, as in the case of S. lividans /pST‐ tleABC , additional peaks with UV spectra similar to that of 3 were observed. NMR and HRMS analyses of each isolated peak revealed that they were new natural indole esters: acetylvalindolmycin ( 7 , reported as a synthetic intermediate), propionylvalindolmycin ( 8 ), and isobutyrylvalindolmycin ( 9 ; Scheme , Supporting Information). These compounds are probably shunt products of the endogenous acylation of 3 , and this was confirmed by feeding of 3 to the S. albus G153/pCCST control strain.…”

Synthetic Indolactam V Analogues as Inhibitors of PAR2‐Induced Calcium Mobilization in Triple‐Negative Breast Cancer Cells

“…As shown in Scheme , the resulting greatly improved synthesis of 1 commenced with the SES protection of 4 followed by reduction of the nitro group of 7 through catalytic hydrogenation. The resulting aniline 8 was then converted into the valine derivative 9 by S N 2 alkylation in virtually quantitative yield . The acid‐catalyzed hydrolysis of the cyclic N , O ‐acetal afforded the desired product 11 besides significant amounts of the double‐deprotected byproduct 10 , which, however, was easily re‐protected with Boc 2 O/NEt 3 to afford 11 in 91 % combined yield from 9 .…”

“…as most promising (Scheme ). Key elements of this approach are the assembly of the nitroindole derivative 4 from building blocks 5 and 6 followed by conversion of the nitro group into a valinyl moiety and closure of the nine‐membered ring through intramolecular peptide coupling …”

“…l-N-methylvaline-containing bridge forming an ine-membered ring. Due to their powerful biological activity andt heir limited accessibility from natural sources,s everalt otal syntheses of in-dolactamV (1) [18][19][20][21][22][23][24][25][26][27][28][29][30][31] and teleocidins [32][33][34][35][36][37][38] have been developed, and an umber of studies using total synthetic analogues have contributed to the profiling of indolactam-V-related or -derived compounds with respecttoP KC activation. [13,39] In contrast to these previous studies, the main goal of the present work was to synthesize and investigate novel indolactam Va nalogues with respect to their PAR2-inhibiting properties.…”

Synthesis of Natural and Unnatural Cyclooligomeric Depsipeptides Enabled by Flow Chemistry

“…The 1 H and 13 C data were in agreement with that reported in the literature . R f =0.29 [40–60 petroleum ether/diethyl ether=10:1]; [ ]=+17.8 ( c 3.35 EtOH) literature; [ ]=+15.4 ( c 2.1, EtOH); 1 H NMR (400 MHz, [D 6 ]DMSO): δ =7.49–7.26 (m, 5 H, C1′c H –C1′e H ), 5.32 (br s., 1 H, C2O H ), 5.25–5.02 (m, 2 H, C1′a H 2 ), 3.86 (d, J =5.0 Hz, 1 H, C2 H ), 2.04–1.81 (m, 1 H, C3 H ), 0.87 (d, J =6.9 Hz, 3 H, C4 H 3 ), 0.81 ppm (d, J =6.9 Hz, 3 H, C4 H 3 ); 13 C NMR (151 MHz, [D 6 ]‐DMSO): δ =172.5 (quat., C 1), 135.6 (quat., C 1′b), 127.6, 127.5, 127.2 (5×CH, C 1′c– C 1′e), 74.7 (CH 2 , C 1′a), 64.8 (CH, C 2), 31.1 (CH, C 3), 17.7 (CH 3 , C 4), 16.3 ppm (CH 3 , C 4).…”