Chemical Synthesis of Coelenterazine and Its Analogs: New Route toward Four Segment-Couplings

Synthesis of chiral hexynones for use as precursors to native photosynthetic hydroporphyrins

“…Second, pentynamide 13 was treated with lithiated methoxymethyl(phenyl)sulfane at −78 °C 64 to give 16 as a mixture of diastereomers (1 : 0.3 ratio) in 43% yield. Treatment of 16 with CuCl 2 /CuO 64 or HgCl 2 /HgO 67 in refluxing anhydrous methanol gave a complex mixture.…”

“…Second, pentynamide 13 was treated with lithiated methoxymethyl(phenyl)sulfane at −78 °C 64 to give 16 as a mixture of diastereomers (1 : 0.3 ratio) in 43% yield. Treatment of 16 with CuCl 2 /CuO 64 or HgCl 2 /HgO 67 in refluxing anhydrous methanol gave a complex mixture. The oxothioacetal 16 upon treatment with 3 equivalents of PIFA in anhydrous methanol gave only ∼50% conversion (on the basis of 1 H NMR analysis), and the mixture of 16 and 7 (1 : 1 ratio) was inseparable by conventional silica gel chromatography.…”

“…Following a reported procedure, 64 a solution of (methoxymethyl)(phenyl)sulfane (231.3 mg, 1.500 mmol) in 10 mL of freshly distilled THF at −78 °C under argon was treated dropwise with n -BuLi (600 μL, 1.5 mmol, 2.5 M in hexanes) for 5 min, and stirred for 1 h at the same condition. Then, the resulting solution was treated dropwise with a solution of 13 (255.4 mg, 0.9999 mmol) in 10 mL of freshly distilled THF, and stirred at −78 °C.…”

“…1 H NMR (500 MHz, CDCl 3 ) d 0.14 (s, 9H), 1.01 (t, J = 7.4 Hz, 3H), 1.17 (d, J = 6.7 Hz, 3H), 1.45-1.30 (m, 1H), 1.63 (dt, J = 13.4, 7.4, and 3.7 Hz, 1H), 2.06-1.95 (m, 1H), 2.11 (dddd, J = 11.1, 5.2, 4.0, and 2.7 Hz, 1H), 2.65-2.42 (m, 3H), 3.00-2.89 (m, 2H), 3.39 (ddd, J = 14.2, 12.0, and 2.7 Hz, 1H), 4.45 (s, 1H); 13 (3R,4R)-4-Ethyl-1-methoxy-3-methyl-1-(phenylthio)-6-(trimethylsilyl)hex-5-yn-2-one (16). Following a reported procedure, 64 a solution of (methoxymethyl)(phenyl)sulfane (231.3 mg, 1.500 mmol) in 10 mL of freshly distilled THF at À78 1C under argon was treated dropwise with n-BuLi (600 mL, 1.5 mmol, 2.5 M in hexanes) for 5 min, and stirred for 1 h at the same condition. Then, the resulting solution was treated dropwise with a solution of 13 (255.4 mg, 0.9999 mmol) in 10 mL of freshly distilled THF, and stirred at À78 1C.…”

“…Such failures of transacetalization of the dithiane group of analogues of 15 are known. [63][64][65] Recourse was achieved by reduction of 15 with NaBH 4 to obtain 5-R in nearly quantitative yield. The newly formed stereocenter (carbinol) was assigned by comparing the 1 H NMR spectrum of 5-R with the reported spectrum of the same compound.…”