Expedient Synthetic Transformation of Ptychantins into Forskolin

Abstract

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 Δ^9,11-enol ether.

Key words

terpenoids - total synthesis - forskolin - labdane diterpenoid

References and Notes

• 1 Bhat SV. Bajwa BS. Dornauer H. de Souza NJ. Fehlhaber HW. Tetrahedron Lett.  1977,  18:  1669 
• 2 Bhat SV. Dohadwalla AN. Bajwa BS. Dadkar NK. Dornauer H. de Souza NJ. J. Med. Chem.  1983,  26:  486 
• 3a Abbadi M. Morin C. Bioorg. Med. Chem. Lett.  1999,  9:  1779 
• 3b Laurenza A. Sutkowski ME. Seamon KB. Trends Pharm. Sci.  1989,  10:  442 
• 4 Ziegler FE. Jaynes BH. Salndane MT. J. Am. Chem. Soc.  1987,  109:  8115 
• 5 Hashimoto S. Sakata S. Sonegawa M. Ikegami S. J. Am. Chem. Soc.  1988,  110:  3670 
• 6a Corey EJ. Da Silva Jardine P. Rohloff JC. J. Am. Chem. Soc.  1988,  110:  3672 
• 6b Corey EJ. Da Silva Jardine P. Tetrahedron Lett.  1989,  30:  7297 
• 7a Delpech B. Calvo D. Lett R. Tetrahedron Lett.  1996,  37:  1015 
• 7b Delpech B. Calvo D. Lett R. Tetrahedron Lett.  1996,  37:  1019 
• 7c Calvo D. Port M. Delpech B. Lett R. Tetrahedron Lett.  1996,  37:  1023 
• 8 Hagiwara H. Takeuchi F. Kudou M. Hoshi T. Suzuki T. Hashimoto T. Asakawa Y. J. Org. Chem.  2006,  71:  4619 
• 9 Hashimoto T. Horie M. Toyota M. Taira Z. Takeda R. Tori M. Asakawa Y. Tetrahedron Lett.  1994,  35:  5457 
• 10 Hrib NJ. Tetrahedron Lett.  1987,  28:  19 
• 11 Khandelwal Y. Morares G. de Souza NJ. Fehlhaber HW. Paulus EF. Tetrahedron Lett.  1986,  27:  6249 

12

Compounds 9-18 have satisfactory ¹H NMR, ¹³C NMR, IR, and high-resolution mass spectral data along with optical rotation values.