Triols, oxidative cleavage

The next key step, the second dihydroxylation, was deferred until the lactone 82 had been formed from compound 80 (Scheme 20). This tactic would alleviate some of the steric hindrance around the C3-C4 double bond, and would create a cyclic molecule which was predicted to have a greater diastereofacial bias. The lactone can be made by first protecting the diol 80 as the acetonide 81 (88 % yield), followed by oxidative cleavage of the two PMB groups with DDQ (86% yield).43 Dihydroxylation of 82 with the standard Upjohn conditions17 furnishes, not unexpectedly, a quantitative yield of the triol 84 as a single diastereoisomer. The triol 84 is presumably fashioned from the initially formed triol 83 by a spontaneous translactonization (see Scheme 20), an event which proved to be a substantial piece of luck, as it simultaneously freed the C-8 hydroxyl from the lactone and protected the C-3 hydroxyl in the alcohol oxidation state. 

The wrong stereochemistry at C(2) was corrected at this stage by selective oxidative cleavage of the O-benzylether followed by inverting the resulting P-alcoho 41, by Mitsunobu reaction to the corresponding a-benzoate 42. Sequential hydrolysis of 42, first by basic methanol, and then with acid provided a triol which was converted into the corresponding triacetate 43. Exposure of 43 to trifluoroacetic acid liberated tri-O-acetyl-7-deoxynarciclasine, the methanolysis of which furnished (+)-7-deoxynarciclasine (31). 

In the synthesis of verrucarin J (55) by Fraser-Reid and coworkers [62], triol 109 was treated with pyridiniura dichromate (PDC) for 3 days, resulting in oxidative cleavage of the adjacent diol to the corresponding aldehyde and further oxidation of the presumed cyclic hemiacetal intermediate gave 55 in 50% yield (Scheme 37). 

Functional group transformations. Dimethyldioxirane effects conversion of isothiocyanates to isocyanates," TV, Al-dimethylhydrazones of aldehydes to nitriles, and the oxidative cleavage of nitronate ions (Nef reaction) with relative ease. Regioselective oxidation of diols and triols is also achieved. " ... 

Fig. (11) The Wieland-Miescher Ketone (1) is converted to keto glycol (125) and then to acetonide conjugated ketone (128) this on sujection to diels-alder reaction with dimethoxybenzocyclobutene affords the adduct (129) which is converted to the triol (132) by the standard organic reactions. The oxidation and cyclization of (132) yield the fiiran-diketone system (133). Its conversion to (+)-halenaquinone (134) is accomplished by the oxidative cleavage, halenaquinol (135) is obtained by reduction of hal enaquinone (134).

C-Glycosidation of enol silane 279 to lactol acetate 278, prepared from 277 in two steps, furiushed ynone 280 as a single isomer. Reduction of the ketone with L-selectride furnished alcohol 270 with poor selectivity, but the minor isomer can be converted into the desired isomer via the Mitsunobu protocol Dihydroxylation of the terminal alkene, reduction of alkyne, and oxidative cleavage of the resulting triol gave the intermediate hydroxy aldehyde, which was spontaneously transformed into macrolactol 281 as a single diastereomer. 

Addition to 1-atkenes (8, 25). The critical steps in a recent synthesis of aldosterone (4) involve anli-Markovnikov addition of C6H5SeBr to I, oxidation to the allylic bromide, and acetate displacement to give 2. The corresponding 21-monoacctate was converted to the triol 3 (0s04, N-mcthylmorpholine N-oxide). The final steps to 4 involved periodate cleavage and saponification.2... 

Androstenolone, 1, can be transformed microbiologically to the 7a,15a-dihy-droxy derivative 2 by the action of Colletotrichium Uni. During formation of the acetal (3), inversion takes place on C-7. Acidic cleavage of 3 results in the triol, 4, which can also be produced by direct acidic catalysis from 2 [12,13]. After selective protection to the 3/l,15a-dipivalate (5), the 15/1,16/1-methylene compound, 6, can be synthetized, and then stereoselectively transformed to the 5/ ,6/ -epoxide, 7. This reacts with triphenylphosphine and tetrachloromethane in pyridine to produce the 7a-chloro derivative, 8. On treatment with zinc and acetic acid, 8 can be converted to the key compound 9, which has a 5/i-hydroxy-6-ene structure. Compound 9 can then be methylenated stereoselectively in the 6/1,7/1 position by the Simmons-Smith method. The last three steps - 10 —> 11 —> 12 — drospirenone -include the build-up of the spironolactone ring, after which water is lost from the molecule and oxidation affords drospirenone. 

Mitsunobu reaction as well as by mesylation and subsequent base treatment failed, the secondary alcohol was inverted by oxidation with pyridinium dichromate and successive reduction with sodium borohydride. The inverted alcohol 454 was protected as an acetate and the acetonide was removed by acid treatment to enable conformational flexibility. Persilylation of triol 455 was succeeded by acetate cleavage with guanidine. Alcohol 456 was deprotonated to assist lactonization. Mild and short treatment with aqueous hydrogen fluoride allowed selective cleavage of the secondary silyl ether. Dehydration of the alcohol 457 was achieved by Tshugaejf vesLCtion. The final steps toward corianin (21) were deprotection of the tertiary alcohols of 458 and epoxidation with peracid. This alternative corianin synthesis needed 34 steps in 0.13% overall yield. 

Fig. 10 (b). The sequence leading to the oxidation and cleavage of the side chain of 5P-cholestane-3a,7a,12a-triol pathway for side-chain cleavage in cholic acid biosynthesis. 

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