Synthesis of 6-oxy functionalized campest-4-en-3-ones: efficient hydroperoxidation at C-6 of campest-5-en-3-one with molecular oxygen and silica gel.
As a reference compound library for the investigation of biosynthesis of brassinosteroids, focused on a pathway from campesterol (1) to campestanol (2), 6-oxy functionalized campest-4-en-3-ones as well as campest-5-en-3-one (7) and campestane-3,6-dione were prepared from 1. Oxidation of 1 with pyridinium chlorochromate buffered by calcium carbonate gave 5-en-3-one (7) in 76% yield. Treatment of 7 with silica gel under an oxygen atmosphere in ethyl ether at room temperature produced efficient hydroperoxidation at the C-6 position to give 6alpha-hydroperoxycampest-4-en-3-one and 6beta-hydroperoxycampest-4-en-3-one in 34% and 49% yields, respectively. These compounds were converted to 6alpha-hydroxycampest-4-en-3-one and 6beta-hydroxycampest-4-en-3-one by reduction with triethyl phosphite. This provided the first example of the practical use of hydroperoxidation at C-6 of a Delta(5(6))-unsaturated 3-oxo-steroid with molecular oxygen and silica gel. On the other hand, oxidation of 1 with pyridinium chlorochromate in the absence of calcium carbonate gave campest-4-ene-3,6-dione in 64% yield. This compound was then converted in a highly stereoselective manner to campestane-3,6-dione with A/B trans ring junction by reduction with titanium (III) chloride in 85% yield.
Seto
H
H
The Institute of Physical and Chemical Research (RIKEN), Wako-shi, 351-0198, Saitama, Japan. hseto@postman.riken.go.jp
Fujioka
S
S
Takatsuto
S
S
Koshino
H
H
Shimizu
T
T
Yoshida
S
S
D001671:Biochemistry / Q000379:methods*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010100:Oxygen; D010840:Phytosterols / Q000737:chemistry / Q000378:metabolism; D058428:Silica Gel; D012822:Silicon Dioxide / Q000737:chemistry
D010840:Phytosterols; C413894:campest-5-en-3-one; C413895:campestane-3,6-dione; C003535:campestanol; C021273:campesterol; D058428:Silica Gel; D012822:Silicon Dioxide; D002784:Cholesterol; D010100:Oxygen