Total Synthesis of Natural Lembehyne C and Investigation of Its Cytotoxic Properties

Abstract

The first Z-stereoselective method for the synthesis of the natural marine alkynol lembehyne C, containing a 1Z,5Z,9Z-triene moiety, in 41% yield was developed using the new Ti-catalyzed cross-coupling of oxygenated and aliphatic 1,2dienes as the key step. It was found for the first time that lembehyne C exhibits moderate cytotoxicity against Jurkat, K562, U937, and HL60 cancer cells and also efficiently induces apoptosis in Jurkat cells, with the cell death mechanism being activated by the mitochondrial pathway. The lembehyne C inhibition of the cell cycle follows the mitotic catastrophe mechanism.

Total Synthesis of Chatenaytrienins-1, -3 and -4 and Muridienins-1–4 Enabled by C(sp)–C(sp3) Sonogashira Coupling

“…(Z)-Octadec-5-en-1-yne (9) 14a The titled compound 9 was prepared from 17 (256.5 mg, 1.28 mmol) by following similar procedure as described for compound 4 to give 9 (254. (Z)-Docos-5-en-1-yne (11) 19 The titled compound 11 was prepared from 19 (328 mg, 1.28 mmol) by following similar procedure as described for compound 4 to give 11 (311.9 mg, 80% over two steps from 19) as a colorless oil.…”

NHC and visible light-mediated photoredox co-catalyzed 1,4-sulfonylacylation of 1,3-enynes for tetrasubstituted allenyl ketones

“…In this regard, in situ generated allene radicals undergo cyanation, 15 a – d arylation, 15 e – i halogenation, 15 j alkynylation, 15 k trifluoromethylation, 15 l or intramolecular cyclization 15 m to afford functionalized allenes. Radical acylation of 1,3-enynes may provide straightforward access to value-added allenyl ketone units, 11 which are a crucial core in important nature products 16 and synthetic intermediates. 17 However, radical acylation of 1,3-enynes has been much less developed and is limited to carboacylation, 11 mainly due to the lack of an efficient acyl transfer approach.…”

DFT mechanistic investigation of the 1,2‐reduction of α,β‐unsaturated ynones

“…The importance of the resulting α,β-unsaturated alcohols (3) is irrefutable, as they serve as essential intermediates in organic syntheses [1][2][3][4][5][6][7][8] and might possess biological activity. [9][10][11][12][13][14][15][16][17] These reactions utilize mostly transition metals as catalysts [18][19][20][21][22][23][24] and often require unfavorable conditions. [22][23][24][25][26][27] Although, there is evidence of chemoselective reductions at room temperature with easily attainable reagents.…”

“…One such example is the reduction of α,β‐unsaturated ynones ( 1 ). The importance of the resulting α,β‐unsaturated alcohols ( 3 ) is irrefutable, as they serve as essential intermediates in organic syntheses [1–8] and might possess biological activity [9–17] . These reactions utilize mostly transition metals as catalysts [18–24] and often require unfavorable conditions [22–27] .…”