- A Radical-Polar Crossover Annulation to Access Terpenoid Motifs
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A new catalytic radical-polar crossover annulation between two unsaturated carbonyl compounds is described. The annulation proceeds under exceptionally mild conditions and provides direct and expedient access to complex terpenoid motifs. Application of this chemistry allows for synthesis of forskolin, a densely functionalized terpenoid, in 14 steps from commercially available material.
- Thomas, William P.,Schatz, Devon J.,George, David T.,Pronin, Sergey V.
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supporting information
p. 12246 - 12250
(2019/08/27)
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- A Concise Synthesis of Forskolin
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A 24-step synthesis of (±)-forskolin is presented, which delivered hundred milligram quantities of this complex diterpene in one pass. Transformations key to our approach include: a) a strategic allylic transposition, b) stepwise assembly of a sterically encumbered isoxazole ring, and c) citric acid-modified Upjohn dihydroxylation of a resilient tetrasubstituted olefin. The developed route has exciting potential for the preparation of new forskolin analogues inaccessible by semisynthesis.
- Hylse, Ond?ej,Maier, Luká?,Ku?era, Roman,Pere?ko, Tomá?,Svobodová, Aneta,Kubala, Luká?,Paruch, Kamil,?venda, Jakub
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p. 12586 - 12589
(2017/09/12)
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- Expedient synthetic transformation of ptychantins into Forskolin
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Forskolin has been synthesized in 11 steps with a 17% overall yield from ptychantins A and B, which have been isolated from the liverwort Ptychanthus striatus in good yield. The 1α-hydroxy group was furnished by stereoselective reduction of the corresponding carbonyl group by sodium cyanoborohydride. The 9α-hydroxy group was introduced stereoselectively by epoxidation of Δ9,11-enol ether. Georg Thieme Verlag Stuttgart.
- Hagiwara, Hisahiro,Tsukagoshi, Masashi,Hoshi, Takashi,Suzuki, Toshio,Hashimoto, Toshihiro,Asakawa, Yoshinori
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p. 929 - 931
(2008/12/22)
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- Synthetic transformation of ptychantin into forskolin and 1,9-dideoxyforskolin
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Forskolin (1), a highly oxygenated labdane diterpenoid and an activator of adenylate cyclase, has been synthesized in 12 steps and 12% overall yield from ptychantin A (4), which has been isolated from liverwort Ptychanthus striatus in good yield. The 1α-hydroxy group was furnished by stereoselective reduction of the corresponding carbonyl group by sodium in t-BuOH. The 9α-hydroxy group was introduced stereoselectively by epoxidation of Δ9.11-enolether. 1,9-Dideoxyforskolin (2), an inhibitor of glucose transporter, has been synthesized in 8 steps and 37% overall yield. The hydroxy group at C-1 was removed by solid-state thicarbonylimidazolation and subsequent radical cleavage.
- Hagiwara, Hisahiro,Takeuchi, Fumihide,Kudou, Masaru,Hoshi, Takashi,Suzuki, Toshio,Hashimoto, Toshihiro,Asakawa, Yoshinori
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p. 4619 - 4624
(2007/10/03)
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- Total synthesis of forskolin - Part II
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The further elaboration of the key-intermediate 5 into forskolin 1 has been achieved via two different routes. Key features of this new total synthesis are: 1) the stereospecific formation of the 6β, 7β, 8α-triol via the BF3-Et2O assisted opening of the epoxy carbamate 8; 2) use of the 8α, 11-di-t-butylsilylene ketal for the specific protection of the 6β, 7β-diol, from the tetrol 10(A); two new sequences for the formation of the dihydro-γ-pyrone ring in high overall yield from 23; 4) the stereoselective divinyl cuprate conjugate α-addition on the dihydro-γ-pyrone 16 or 28, in the presence of BF3-Et2o, with the stereochemistry required for forskolin synthesis.
- Delpech, Bernard,Calvo, Daniel,Lett, Robert
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p. 1019 - 1022
(2007/10/03)
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- Regioselective acetylation of 7-deacetylforskolin with 11C-acetyl chloride
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Reaction conditions were studied to control the acetylating position on 7-deacetylforskolin using [11C]acetyl chloride. In a preliminary study using non-labeled acetyl chloride, pyridine, lutidine, triethylamine, N,N-diisopropylethylamine, dimethylaminopyridine (DMAP) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were tested as the base in the acetylation. Pyridine was effective in selective acetylation to yield forskolin in any solvent, and DBU was effective for 1-acetyl-7-deacetylforskolin. Among toluene, dichloromethane and dichloroethane, toluene was the most suitable as the solvent for the selective acetylation of the 7-OH group to give forskolin with any base. In the selectivity of acetylation with [11C]acetyl chloride, more [11C]forskolin was obtained than [11C]1-acetyl-7-deacetylforskolin (70:30) in the presence of pyridine in toluene. [11C]1-acetyl-7-deacetylforskolin was preferentially synthesized with DBU in dichloromethane, and the ratio of [11C]1-acetyl-7-deacetylforskolin to [11C]forskolin was 98:2. For the yield of the [11C]acetylated product, DBU in dichloromethane was also suitable to obtain [11C]1-acetyl-7-deacetylforskolin. However, that of pyridine in toluene did not confer any advantages upon the yield of [11C]forskolin compared with DMAP in toluene.
- Sasaki,Furukata,Ishii,Iimori,Ikegami,Nozaki,Senda
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p. 337 - 347
(2007/10/03)
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- Pharmaceutical compositions comprising labdane diterpenoid derivatives and pyrimido(6,1-a)isoquinolin-4-one derivatives and their use
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Pharmaceutical compositions comprising labdane diterpenoid derivatives and pyrimido(6,1-a)-isoquinolin-4-one derivatives when administered to the skin of a mammal or of the man increase the rate of terminal hair growth, stimulate the conversion of vellus hair to growth as terminal hair and arrest hair loss. They can be used for the treatment of several kinds of alopecia.
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- SPIROFORSKOLIN: ACID-CATALYZED REARRANGEMENT PRODUCT OF FORSKOLIN
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Lewis acid induced carbocation mediated rearrangement of forskolin (1) afforded a spirolabdane, designated as spiroforskolin (2).
- Vishwakarma, R. A.
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p. 131 - 132
(2007/10/02)
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