64657-20-1Relevant academic research and scientific papers
Stability of forskolin in lipid emulsions and oil/water partition coefficients
Yamamura,Nakao,Yano,Miyamoto,Yotsuyanagi
, p. 1032 - 1034 (1991)
Forskolin (FK), a diterpenoid isolated from Coleus Forskohlii, underwent base-catalyzed hydrolysis, producing 7-deacetyl forskolin. The half-life at pH 7.0 and 25°C was 16 d. Because of its poor solubility in water and degradation, the drug was incorporated in lipid emulsions (soybean oil/water=10.9/89.1 v/v, average diameter of the droplets, 204 nm). No degradation of the drug was found in the lipid emulsion up to 30 d. The distribution of FK in the lipid emulsions was investigated based on a three-phase model which assumes that the drug resides in the oil and water phases and at the oil/water interface. From the determination of bulk oil/water and lipid emulsion partition coefficients, the relative percentages of the drug in the oil droplets, in the aqueous phase and at the interface were 43.3, 4.9 and 51.3%, respectively. This distribution profile seems to be consistent with the improved stability of FK in the lipid emulsions where the drug residing in the oil phase and at the interface is well protected from hydrolysis. The FK lipid emulsions should be given more interest in access to preclinical and clinical tests because the drug was well stabilized in the formulation and the excipients used are acceptable to human subjects.
RECONSTITUTION OF FORSKOLIN FROM A RING C DIHYDROPYRAN-4-ONE DEGRADATION PRODUCT THEREOF
Ziegler, Frederick E.,Jaynes, Burton H.
, p. 2339 - 2342 (1987)
Dihydropyran-4-one 2b, derived from the known degradation product 2a of forskolin 1, has been successfully converted into forskolin by a photochemical route.
A Radical-Polar Crossover Annulation to Access Terpenoid Motifs
Thomas, William P.,Schatz, Devon J.,George, David T.,Pronin, Sergey V.
supporting information, p. 12246 - 12250 (2019/08/27)
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.
A Concise Synthesis of Forskolin
Hylse, Ond?ej,Maier, Luká?,Ku?era, Roman,Pere?ko, Tomá?,Svobodová, Aneta,Kubala, Luká?,Paruch, Kamil,?venda, Jakub
, p. 12586 - 12589 (2017/09/12)
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.
Ethylenediamine: An effective reagent for deacetylation of natural products
Mohankumar, Ramasamy,Ilango, Kaliappan,Santhanakrishnan, Vichangal Pridiuldi,Radhakrishnan, Viswanathan,Narasimhan, Srinivasan
experimental part, p. 851 - 858 (2010/12/25)
The use of ethylenediamine in methanol is described for the selective cleavage of the acetate group in nimbin (1) to 6-deacetyl nimbin (1a) under microwave irradiation. This method enables to deacetylate without affecting other functional groups such as ,α,β-unsaturated ketone, ester, ether, etc. in certain tetranortriterpenoids and other acetate-containing natural compounds.
Expedient synthetic transformation of ptychantins into Forskolin
Hagiwara, Hisahiro,Tsukagoshi, Masashi,Hoshi, Takashi,Suzuki, Toshio,Hashimoto, Toshihiro,Asakawa, Yoshinori
, p. 929 - 931 (2008/12/22)
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.
Synthetic transformation of ptychantin into forskolin and 1,9-dideoxyforskolin
Hagiwara, Hisahiro,Takeuchi, Fumihide,Kudou, Masaru,Hoshi, Takashi,Suzuki, Toshio,Hashimoto, Toshihiro,Asakawa, Yoshinori
, p. 4619 - 4624 (2007/10/03)
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.
Total synthesis of forskolin - Part II
Delpech, Bernard,Calvo, Daniel,Lett, Robert
, p. 1019 - 1022 (2007/10/03)
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.
NOVEL 1,9-DIDEOXYFORSKOLIN ANALOGUES THROUGH MICROBIAL TRANSFORMATIONS
Khandelwal, Y.,Inamdar, P. K.,Souza, N. J. de,Rupp, R. H.,Chatterjee, S.,Ganguli, B. N.
, p. 1661 - 1666 (2007/10/02)
Microbial transformations of 1,9-dideoxyforskolin (1) and 7-deacetyl-1,9-dideoxyforskolin (2) were carried out.Various mono- and di-hydroxylated derivatives were isolated and identified.
