66428-89-5

Upstream product

• 108-24-7 acetic anhydride 
• 64657-20-1 (+/-)-desacetyl forskolin 
• 13051-32-6 dimethyl 2,2-dimethylglutarate 
• 114375-41-6 (3aβ,5aβ,6aα,9aα,9bα,9cβ)-Decahydro-1,1,8,8,9c-pentamethyl-6-methylene-5H-furo<4',3',2':4,5>naphtho<1,2-d><1,3>dioxol-5-one 
• 111901-54-3 (3aβ,,6aα,9aα,9bβ,9cβ)-1,2,3,3a,6a,9a,9b,9c-Octahydro-1,1,6,8,8,9c-hexamethyl-5H-furo<4',3',2':4,5>naphtho<1,2-d><1,3>dioxol-5-one 
• 114375-37-0 (2aR,3R,5aR,8aR,8bR)-3-Methoxy-6,6,8b-trimethyl-2a,3,5a,6,7,8,8a,8b-octahydro-naphtho[1,8-bc]furan-2-one 
• 141424-11-5 4,4-dimethyl-5-(tetrahydro-2H-pyran-2-yloxy)pentanal 

Downstream Products

• 64657-20-1 7-deacetyl forskolin 
• 64657-11-0 C₂₂H₃₄O₇ 
• 66575-29-9 forskolin 

Relevant academic research and scientific papers

A Radical-Polar Crossover Annulation to Access Terpenoid Motifs

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

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.

Total synthesis of forskolin - Part II

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.