Lactones osmium tetroxide

One way in which the Z-a,P-unsaturated carbonyl functionality could be exploited would be via its incorporation into lactone 17. It could be predicted with some confidence that external reagents would attack the bicyclic lactonic system from its convex face. Such an a attack by osmium tetroxide would provide the correct 7,8-erythro diol stereochemistry required to reach NeuSAc. This anticipation turned out to be well founded. 

The method by which lactone 17 was obtained was not without its own implications for the synthesis. Treatment of 16 with dry tetra n-butylammonium fluoride in acetonitrile achieved desilylation. Not unexpectedly, this process triggered migration of the C5 benzoyl group to the newly unveiled C4 alcohol. The C5 alcohol thereby liberated underwent lactonization to the desired 17 (61% yield from 16). Indeed, reaction of 17 with stoichiometric osmium tetroxide in pyridine-THF afforded a single diol formulated as 18 in 97% yield (see Figure 4). 

Oxandrolone Oxandrolone, 17j3-hydroxy-17a-methyl-2-oxa-5-androstan-3-one (29.3.10), is made by oxidation of the C1-C2 double bond of 17j3-hydroxy-17a-methyl-l-androsten-3-one by a mixture of lead tetraacetate and osmium tetroxide with an opening of the A ring of the steroid system, which forms an aldehyde acid (29.3.9). Upon reducing the aldehyde group with sodium borohydride, intramolecular cyclization takes place, directly forming a lactone (29.3.10), which is the desired oxandrolone [31,32]. 

The lactone (464) was reduced with lithium aluminium hydride to the (20/ )-18,20-diol. Regeneration of the A -3-keto-group afforded the keto-diol (465). Catalytic hydrogenation in alkaline medium selectively reduced the double bond at C(4) and gave the desired configuration of 5)5-H. Acetylation at C(18) was followed by oxidation, which provided the diketo-pregnane (466). Hydroxy-la tion of the -double-bond of (466) with osmium tetroxide gave the 3a,9a-... 

Further degradation of [n, R = H and R = CH3] has been achieved as follows. Oxidation of [ii, R = H] with osmium tetroxide afforded 6-y-hydroxy-13-(a /hdihydroxyethyl)-octahydromethyhnorphenol [iv, R = H] which was converted to 6-y-hydroxy-13-aldehydooctahydromethylmorphenol [v, R = H], which resisted all attempts at direct oxidation to the acid. However the oxime [vi, R = H] was dehydrated to 6-y -acetoxy-13 - cyano octahydromethylmorphenol [vii, R = Ac] hydrolysis of which afforded 6-y-hydroxy-13-carboxyoctahydromethylmorphenol [vni, R = H]. This sequence of reactions was repeated with [ii, R = CH3] giving [iv, R = CHS]-[vi, R — CH3] and with 6-a-hydroxy- and 6-a-methoxy- 13-vinyloctahydro-methylmorphenol obtained from a-tetrahydrocodeimethine. [vin, R = H] could not be lactonized. 

Among these extensive studies, the first total synthesis of ( )-pan-cratistatin (211) has been reported (J49) (Scheme 20). Tricyclic 1,2-dihydroxy-5-lactone 214 was converted into vicinal acetoxy-bromo-5-lactone 215 in 88% yield along with the regioisomers. Osmium tetroxide oxidation of 215, followed by introduction of a double bond and selective protection of the hydroxyl groups, gave the corresponding allylic alcohol... 

The second method uses the pregnane derivative XI as a starting material. This compound, on hydroxylation with osmium tetroxide, afforded the diol Xlla. This diol was then converted to the androstane analogue X. The same approach was independently published also by Hondo and Mori (3). As a by-product of hydroxylation of olefin XI with osmium tetroxide, we obtained 2B,3B-diol XIV and, from this, the lactone XV. However, when we treated XII (a corresponding diacetate, respectively) with trifluoroperacetic acid we found that oxidation of the side chain surprisingly proceeded much faster than oxidation of the B ring. Thus we obtained not only compound X but also an intermediate, compound XHIb, and on hydrolysis compound Xllla, that is the androstane analogue of castasterone ... 

Silylation of 276 with TBSOTf furnishes the bis-TBS ether, which undergoes an osmium tetroxide hydroxylation to afford the syn,anti,syn,anti,syn- iQi o 278 in 73% yield and with high diastereoselectivity. Selective diol oxidative cleavage with periodic acid, PCC oxidation of the resulting epimeric lactols to the lactone, followed by deprotection with /7-toluene-... 

Osmium tetroxide-catalyzed dihydroxylation followed by treatment with N-methyhnorpholine AT-oxide gave the lactone (4S)-168 in 78% yield. Treatment of (4S)-168 with chloromethyl methyl ether furnished the di-MOM ether (4S)-169 in 78% yield. Reduction of (4S)-169 with Dibal-H gave the (4S)-diol 39 in 81% yield, which can be converted into (-)-anisomycin (1) [52]. 

To construct tricycHc compound 275, they first employed sodium boro-hydride to reduce the keto group to furnish alcohol 273. The terminal olefin was then converted to an alcohol via a two-step protocol employing oxidation with osmium tetroxide and sodium periodate followed by reduction with sodium borohydride to furnish diol 274, which underwent acid mediated lactonization. Dess—Martin oxidation of the remaining secondary alcohol then led to the desired tricyclic lactone 275. 

The lactone derivatives (369) prepared from L-glutamic acid (2-amino-2,3,4-trideoxy-L- /ycero-pentaric acid) can be converted into the 5,5-di-C-methylpent-ose derivative (370) by the reactions outlined in Scheme 65. A salient feature of the synthesis is that the chirality of L-glutamic acid is preserved at C-2 of (370). The enone (371) [prepared from 2-(2-furyl)propan-2-ol] has been converted into methyl 2,3-0-isopropylidene-5,5-di-C-methyl-P-DL-ribopyranoside (372) by cis-dihydroxylation (silver chlorate-osmium tetroxide) and stereoselective reduction (lithium aluminium hydride) of the 2,3-0-isopropylidene derivative of the resulting diol. ... 

Anhydro-l,4-di-0-benzyl-L-threitol on reaction with allylmagnesium bromide, osmium tetroxide, sodium periodate then HCl affords methyl 3-C-(benzyloxymethyl)-2,3-dideoxy-L-r/ireo-pentofuranoside as a useful intermediate for the synthesis of 2 3 -dideoxy-3 -C-(hydroxymethyl)-4 -thionucleosides. In an alternative route to such nucleosides the intermediate branched-sugar 50 was prepared in which the hydroxymethyl group was introduced into the 3-position by a light-induced addition of methanol to 6-O-rerr-butyldimethylsilyl-D-g/yceru-pent-2-eno-1,4-lactone (see Vol. 26, p. 242, ref. 159). ... 

A cyclopropane ring was also apparent in the pmr spectrum of (55). Oxidation of (55) with osmium tetroxide followed by lead tetraacetate gave a new y-lactone (57) (Fig. 23) with the same structure as (55) at C-7 through C-15. Inclusion of the cyclopropane ring completes the assignment of structure to (57), while consideration of the groups lost in the oxidation allows assignment of (55). 

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