Synthesis of novel 1,2,3-triazolyl derivatives of pregnane, androstane and D-homoandrostane. Tandem "click" reaction/Cu-catalyzed D-homo rearrangement.
Copper-catalyzed 1,3-dipolar cycloaddition has been employed in the reaction of steroidal azides with various terminal alkynes. A number of novel 1,2,3-triazolyl derivatives of pregnane, androstane and D-homoandrostane were obtained in high yield (70-98%). The developed synthetic protocols allowed us to attach the triazolyl moiety to both the side chain and the steroidal backbone directly, despite the steric hindrance exerted by the polycyclic system. The presence of Cu(II) was shown to evoke d-homo rearrangement under mild conditions. A rational choice of the copper precatalyst permitted us to carry out the "click" reaction either along with tandem d-homo rearrangement or in the absence of this process. The tendency of 16-heterosubstituted steroids to undergo D-homo rearrangement under Cu(II) catalysis was studied.
Chemistry Department, M. V. Lomonosov Moscow State University, 1/3 Leninskiye Gory, Moscow 119991, Russia. nvluk@org.chem.msu.ru.
Yury N
YN
Kotovshchikov
Gennadij V
GV
Latyshev
Nikolay V
NV
Lukashev
Irina P
IP
Beletskaya
D015113:Androstane-3,17-diol / Q000138:chemical synthesis* / Q000737:chemistry; D000731:Androstanes / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D057930:Click Chemistry / Q000379:methods*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D006718:Homosteroids / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D011278:Pregnanes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry
D000731:Androstanes; D006571:Heterocyclic Compounds; D006718:Homosteroids; D011278:Pregnanes; D014230:Triazoles; D015113:Androstane-3,17-diol; D003300:Copper; D013254:Steroid 17-alpha-Hydroxylase; C033936:androstane