2a-Methyl-5a-cholestane

Rao prepared 2a-methyl-5a-cholestan-2i -ol (5) by reaction of methyl-magnesium iodide with 5a-cholestan-2-one (4). The 2i -configuration of the hydroxyl group was established by converting (5) to the 2a-methyl-2j5,19-epoxide (6) with lead tetraacetate and iodine in boiling benzene. 

In some cases products of rearrangement are obtained either partially or exclusively on treatment of Grignard reagents with epoxides. Thus, reaction of the 2/ ,3/ -epoxide (14) with methyl Grignard reagent affords a mixture of two epimeric secondary A-nor alcohols (15) in 80% yield and the tertiary hydroxy compound, 2a-methyl-5a-cholestan-2/f-ol (16) in 15 % yield. ... 

A solution of 0.7 g (18 mmoles) of potassium in 35 ml of /-butanol is added to a boiling solution of 5 g (13 mmoles) of 5a-cholestan-3-one in 50 ml of benzene and 25 ml of /-butanol. A total of 5 ml (11.4 g, 80 mmoles) of methyl iodide in 50 ml of benzene is then added and refluxing is continued for 3 min. The solution is cooled, ice is added and the product is isolated by extraction with ether. The crystalline residue in light petroleum solution is chromatographed on 300 g of alumina. Elution with light petroleum yields initially 0.55 g (10%) of 2,2-dimethyl-5a-cholestan-3-one mp 111-113° [o(]d 77° (CHCI3), after crystallization from ether-methanol. Further elution affords 1.01 g (20%) of 2a-methyl-5a-cholestan-3-one mp 119-120° [a]o 32° (CHCI3), after crystallization from ether-methanol. 

The product, isolated as above, is dissolved in pentane solution and chromatographed on 100 g of alumina. The initial fraction eluted with pentane, yields 1.02 g (48%) of 2,2-dimethyl-5a-cholestan-3-one mp 111-113°, after crystallization from ether-methanol. The subsequent fraction, eluted with pentane and pentane-benzene (9 1) gives 0.12 g (6%) of 2a-methyl-5a-cholestan-3-one mp 119-120°, after crystallization from methanol-ether. 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

In addition to 24-epiBR (I), the following compounds were used as standards II, X and (22R,23R,24R)-2a,3a,22,23-tetrahydroxy-24-methyl-5a-cholestan-6-one (XXVII). We found that the activities of the compounds paralleled the... 

In the absence of steric factors e.g. 5 ), the attack is antiparallel (A) (to the adjacent axial bond) and gives the axially substituted chair form (12). In the presence of steric hindrance to attack in the preferred fashion, approach is parallel (P), from the opposite side, and the true kinetic product is the axially substituted boat form (13). This normally undergoes an immediate conformational flip to the equatorial chair form (14) which is isolated as the kinetic product. The effect of such factors is exemplified in the behavior of 3-ketones. Thus, kinetically controlled bromination of 5a-cholestan-3-one (enol acetate) yields the 2a-epimer, (15), which is also the stable form. The presence of a 5a-substituent counteracts the steric effect of the 10-methyl group and results in the formation of the unstable 2l5-(axial)halo ketone... 

Oxidative rearrangement of 5a-cholestan-3-one (62) with hydrogen peroxide and a catalytic amount of selenic acid affords 2a-carboxy-A-nor-5a-cholestane, isolated in about 35 % yield as the methyl ester (63)." However, the reaction gives a complex mixture of A-nor- and seco-acids, and under... 

Reactions involving Enols or Enolic Derivatives.—Polyhalogenation studies on 5/8-cholestan-2-one show that chlorination occurs in the order l/8,3a,3/8, followed in the case of chlorination by the highly hindered la-position. Attempted bromination beyond the 1/8,3,3-tribromide gave only l,l,3-tribromo-5/8-cholest-3-en-2-one. ° Acid-catalysed bromination of la-methyl and la-phenyl-5a-cholestan-3-ones occurred normally to give 2a-bromo-derivatives. The bromination of 5/3-cholestan-3-one at the 4/8-position is also unaffected by the presence of a la-methyl... 

From 40 kg of rape pollen, 4 mg of an active compound was eventually isolated and shown to be the novel plant growth substance brassinolide (1) (3). The structure, as determined by X-ray crystallography, was [ (2a, 3a, 22R, 23R)-tetrahydroxy- 24 a-methyl-B-homo-7-oxa-5a-cholestane-6-one]. This structure was unique in possessing a 24a-methyl, a 7-oxalactonic B ring, and vicinal hydroxyls on the A ring (C2a and C3a) plus a side chain (C22R and C23R ). 

R,23R,24R)-2a,3a,22,23-tetrahydroxy-24-methyl-7-oxa-B-homo-5a-cholestan-6-one) has almost the same activity as BR, we prepared this compound as a standard possessing high specific activity. For the structure-activity relationship studies it was necessary to have also a standard with low specific activity for comparison and we chose a cholestane analogue of BR, compound II (2a,3a-dihydroxy-7-oxa-B-homo-... 

Our experiments were carried out mainly with maize (Zea mays L.) hybrids 171 x 330A and Danyu 13, provided by Shenyang Agricultural University and Shenyang Seed Company. Brassinolide (2a,3a,22R,23R-tetrahydroxy-24S-methyl-B-homo-oxa-5a-cholestan-6-one) (Figure 1), a natural type synthesized by Fugisawa Pharmaceutical Co., Ltd., was... 

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