Total synthesis of (.+-.)-forskolin

Abstract

drolysis, affording the enone 18 as a 64:36 mixture of E to Z isomers in 59% yield. The crucial ring closure of 18 via oxyselenation furnished, after reductive workup, the desired tetrahydropyran-Cone 19 in 78% yield along with 6% yield of its epimer. In stark contrast to the result with a model system,88 the stereochemical outcome of this cyclization proved to be independent of the starting olefin geometry (19 and its epimer: 79% and 5% from E-18; 80% and 6% from 2-18), implying that cyclization proceeded through the chair-preferred transition state involving a stable open carbocation allowing rotation about C-12/C-13 bond to direct the methyl group a t an axial position.

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“…Forskolin is not available by chemical synthesis due to its complicated structure. However, two groups have reported successful total synthesis of forskolin [3,4]. …”

Polarity Matching of Radical Trapping: High Yielding 3‐exo and 4‐exo Cyclizations

“…The following compounds were prepared according to literature procedures, or have already been described in the literature: The following compounds were synthesized according to literature procedures: 1 ,18 17 ,19 18 ,20 23 ,21 25 ,22 27 ,23 36 24…”

“…Isomer ratios were determined by suitable 1 H NMR integrals of cleanly separated signals. NMR: Bruker AMX 300, AM 400; 1 H NMR, [D 5 ]benzene (7.16 ppm) and CHCl 3 (7.26 ppm) in the indicated solvent as internal standard in the same solvent; 13 The following compounds were prepared according to literature procedures, or have already been described in the literature: The following compounds were synthesized according to literature procedures: 1, [18] 17, [19] 18, [20] 23, [21] 25, [22] 27, [23] 36. [24] General procedure 1 (GP 1)…”

“…The solvents were removed under reduced pressure and the crude product purified by silica gel chromatography (CH/EE 49:1) to yield 7 (480 mg, 33 %, dr 10:1). R f = 0.4 (CH/EE 19:1); 1 2,2-Dimethyl-3-propyl-but-3-enoic ethyl ester (19): NaH (661 mg, 28.8 mmol) was suspended in dry DMSO (30 mL) and heated at 70 8C for 1 h. Methyltriphenylphosphonium bromide (10.3 g, 28.8 mmol) in DMSO (30 mL) was added. After 1 h 18 (4.66 g, 25.0 mmol) was added and the reaction mixture was stirred at 55 8C for 16 h. The Reaction was stopped by adding water (60 mL) and extracting with Et 2 O (3 50 mL).…”

An Efficient Method for Selective Deprotection of Trimethylsilyl Ethers, Tetrahydropyranyl Ethers, Ethylene Acetals, and Ketals Under Microwave Irradiation

“…[1][2][3] A wide variety of methods are available for the conversion of alcohols to their trimethylsilyl ethers and tetrahydropyranyl ethers and much attention has been paid to the deprotection of these derivatives to give the parent alcohol or to give their corresponding carbonyl compounds via oxidative cleavage of the protected groups. [1][2][3] A wide variety of methods are available for the conversion of alcohols to their trimethylsilyl ethers and tetrahydropyranyl ethers and much attention has been paid to the deprotection of these derivatives to give the parent alcohol or to give their corresponding carbonyl compounds via oxidative cleavage of the protected groups.…”