O-benzylidene derivatives

Unlike the 4,6-O-benzylidene derivatives, methyl 2,3-O-benzylidene-5-0-methyl-/ -D-ribofuranoside (99) (9) in which the acetal spans two secondary hydroxyl groups, reacts with NBS to give (48) the isomeric bromobenzoates 100 and 101. These are formed in a ratio of 2 1, and,... 

Reaction of 1 with benzaldehyde and zinc chloride gave a diastereomeric mixture (6) of R- and 5-2,3-O-benzylidene derivatives (4a and 4b). The former (4a) would be identical to the acetal described by Zinner et al. (3) as 2,4-O-benzylidene-D-ribono-1,5-lactone. This structure was further established as 4a, by chemical and physical studies of the product obtained on reaction of 1 with benzaldehyde dimethyl acetal (7). The 2,3-O-benzylidene derivative, obtained by Garegg et al. (8) on reaction of 1 with a,a-dichlorotoluene in pyridine, has the same properties as compound 4a, which would indicate the -configuration for the acetal carbon. 

Physical Constants for the Reassigned Structures of O-Benzylidene Derivatives of D-Ribonolactone (1)... 

The procedure was extended to O-benzylidene derivatives of some disaccharides,116-132 2-acetamido-2-deoxyhexopyranosides, 3-azido-3-... 

The synthesis of the partially methylated glucoside, methyl 2,3-di-O-methyl-a-D-glucopyranoside (34) (Expt 5.121) also utilises the 4,6-O-benzylidene derivative (27), which is first converted into the 2,3-di-O-methyl derivative (33) by reaction with dimethyl sulphate in the presence of sodium hydroxide. Selective removal of the acetal grouping is achieved by mild acid hydrolysis the methyl ether groups are stable under both acidic and basic conditions. 

In the synthesis of the glycolipid asialo GMI described by Ogawa and co-workers [107] the trisaccharide derivative (215) (used in the synthesis of asialo GM2) was converted into the 4,6-O-benzylidene derivative (233) and this was condensed with aceto-bromogalactose in the presence of mercury(II) cyanide and molecular sieves to give the P-linked acetylated galactose derivative in 97 % yield. The product was deprotected and acetylated to give the peracetyl derivative (234) of the tetrasaccharide which was converted into the free sugar (235) with hydrazine hydrate. Compound (235) was converted into asialo GMI via the imidate as described above for the synthesis of asialo GM2 from the imidate (219). 

Benzylidene derivatives led to comparable amounts of 3- and 4-deoxy derivatives,26 whereas 4,6-O-benzylidene derivatives of glucose suffer deoxygenation at C-6 via the (less stabilized) primary radical, while the analogous galactose derivative led mainly to the 4-deoxy derivatives. The different regioselectivity has been explained considering the relative strain in the fused bicyclic structures.27... 

The 5,6-O-benzylidene derivative 48 led to 49 and 50 in 4.9 1 ratio by a ringopening redox rearrangement of the benzylidene acetal catalyzed by tri-tert-butoxysilanethiol (Bu SiSH).103... 

Vicinal O-benzylidene derivatives can be opened selectively. Reaction of methyl 2,3 4,6-di-0-benzylidene-a-D-mannoside (230) with butyllithium and... 

The exo and endo isomers of benzylidene acetals of the carbohydrate series can be obtained separately. Their behavior on reduction with HzAlCl accords with the analysis outlined above frequently only one product is obtained. Thus, the 1,2,4,6-di-O-benzylidene derivatives of glucose (42) and (43 R = H or Bn) cleave rapidly with 1 equiv. of H2AICI at 0 °C (30 min for 42 and 10 min for 43) at the marked bonds." Here, at least, it is clear that steric effects outweigh polar ones. The 2,3-endo and -exo isomers of the a-D-mannoside series (44) and (45) likewise cleave mainly equatorial (78 22) and axial (96 4), respectively, when treated with 1 equiv. of H2AICI at room temperature. The same behavior is seen with the methyl 2,3-benzylidene-a-L-rhamnosides," the methyl 3,4-0-benzylidene-P-L-arabinosides" and... 

OH free Here, for all the three monosaccharides, a derivative with the 4-OH free can be obtained from the 4,6-O-benzylidene derivative through regioselective reductive opening. Formation of the 4,6-acetal with consecutive 2,3-protection (acetylation, benzoylation, benzylation) and reductive opening using various reagents yields the desired compounds. In mannosides, the selective formation of the 4,6-6>-acetal is not trivial, but can be accomplished with a 50 to 70% yield. 

Radical-mediated reaction of a radical precursor tetrahydroisoquinoline derivative has been found to produce the 5,11-methanomorphanthridine ring system 182). Thus, a formal total synthesis of this type of alkaloid was performed by means of the present methodology. Namely, the reaction of l,2,3,4-tetrahydro-A -(4-oxocyclohex-2-enyl)-4-phenylthioisoquinoline (357) with BusSnH in boiling o-xylene containing AIBN led to 5,11-methanomorphanthridin-2-one (358) in 80% yield, which was transformed to A -5,ll-methanomorphanthridine 359 by way of a mesate. In continuation, 359 provided the 2,3-O-benzylidene derivative 349 in two steps (OSO4 oxidation and O-benzylidenation), which was previously 179) converted into this type of alkaloid (Scheme 37). 

Foster and coworkers50 established that benzylidenation under these conditions gives rise to diastereoisomeric 2-phenyl-l,3-dioxane derivatives, indicating that kinetic control is operative. They isolated both diastereoisomers of the 4,6-O-benzylidene derivatives of methyl a-D-gluco- and -galacto-pyranoside (as 2,3-di-O-methyl derivatives). 

Other procedures frequently adopted involve periodate oxidation of a suitable acetal derivative,63 and borohydride reduction of acetals of lactones.64 It has also proved feasible to interchange acetals by means of acid catalysis55,56 thus, reaction of a 1,2-O-isopropylidene derivative of D-glucose with benzaldehyde and sulfuric acid afforded the corresponding 1,2-O-benzylidene derivative. 

The first synthesis of gualamycin (1) was achieved from 2 by conversion to the glycosyl acceptor 7 whose glycosidation gave 1 (Schemes 1 and 2). Thus, the di-O-benzylidene derivative 7 was synthesized from compound 4, which was derived from the azido compound 2 through the key intermediate 3. Treatment of 4 with NaaCOs in methanol gave the... 

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