Potential corticoid metabolites: chemical synthesis of 3- and 21-monosulfates and their double-conjugates of tetrahydrocorticosteroids in the 5alpha- and 5beta-series.
Here, we describe the chemical synthesis of the complete sets of 18 novel 3- and 21-monosulfates and their double-conjugated form of tetrahydrocortisol (THF), tetrahydro-11-deoxycortisol (THS), and tetrahydrocortisone (THE) in the 5alpha- and 5beta-series. The principal reactions involved are: (1) selective protection of a specific hydroxy group in substrates; (2) catalytic hydrogenation at C-5 of Delta(4)-3-ketosteroids with 10% Pd(OH)(2)/C to yield 3-oxo-5beta-steroids and reductive allomerization with 10% Pd/C to yield 3-oxo-5alpha-isomers; (3) reduction of the resulting 3-oxo-5beta- and 3-oxo-5alpha-steroids to the corresponding 3alpha-hydroxy-compounds with Zn(BH(4))(2) and K-Selectride((R)), respectively; and (4) sulfation of hydroxy groups at C-3 and/or C-21 in the tetrahydrocorticosteroid derivatives with sulfur trioxide-triethylamine complex.
Okihara
Rika
R
Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka 577-8502, Japan.
Mitamura
Kuniko
K
Hasegawa
Maki
M
Mori
Megumi
M
Muto
Akina
A
Kakiyama
Genta
G
Ogawa
Shoujiro
S
Iida
Takashi
T
Shimada
Miki
M
Mano
Nariyasu
N
Ikegawa
Shigeo
S
D008968:Molecular Conformation; D013237:Stereoisomerism; D013431:Sulfates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013760:Tetrahydrocortisol / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
D013431:Sulfates; D013760:Tetrahydrocortisol