P-methoxybenzyl protected

Treatment of 8-azidomethylperhydropyrido[l,2-c]pyrimidin-l-one 157 with methyl triflate and catalytic hydrogenation of the azide group led to the formation of tricyclic guanidine derivative 158 (01JA8851). Hydroxy group of 149 was protected with methoxymethyl chloride, and the p-methoxybenzyl protecting group (PMB) was eliminated by treatment with DDQ. 

For benzyloxymethyl electrophiles, titanium enolates are superior to the corresponding lithium enolates in both yield and alkylation diastereoselectivity (eq 11). Unfortunately, the analogous p-methoxybenzyl-protected (3-hydroxy adducts cannot be obtained by this method. In other cases the titanium methodology complements the corresponding reactions of the lithium and sodium enolates for SNl-like electrophiles. It is noteworthy that imides may be selectively enolized under all of the preceding conditions in the presence of esters (eq 12). 

This particular reaction allowed us to carry out the hitherto shortest synthesis of erythronolide A. The efficiency of this synthesis is clearly a consequence of both the stereoselective chain extension processes as well as the advantageous use of p-methoxybenzyl protective groups. 

The p-methoxybenzyl protecting group in tetrazole 401 was hydrogenolyzed without the cleavage of the hydroxy group (Scheme 119).ti i... 

The precursor (121) for the A-ring was prepared in three steps from aldehyde (120). This compound was condensed with ketone (119) in a Borsche modification of the Friedlander reaction to give tetracyclic quinoline (122) (Scheme 18). Selective cleavage of the A-ring p-methoxybenzyl protecting group allowed further transformation to nitro compound (123). 

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

NaH, /7-MeOQH4CH2Br, DMF, —5°, 1 h, 65%. Other bases, such as BuLi, ° dimsyl potassium," and NaOH under phase-transfer conditions," have been used to introduce the MPM group. The use of (n-Bu)4N I for the in situ preparation of the very reactive p-methoxybenzyl iodide often improves the protection of hindered alcohols." In the following example, selectivity is probably achieved because of the increased acidity of the 2 -hydroxyl group ... 

Protection of alcohols. Even somewhat hindered secondary alcohols or tertiary alcohols are converted into (p-methoxybenzyloxy)methyl (PMBM) ethers by reaction with 1 and diisopropylethylamine in CH2C12 for 3-30 hours. Deprotection can be effected by oxidation with DDQ (65-95% yield), a method previously recommended for deprotection of p-methoxybenzyl ethers (11, 166-167). 

An intramolecular acetal has also been introduced by the treatment of a mixture of a 1-thio-mannoside, having a methoxybenzyl protecting group at C-2 and an alcohol with DDQ [71] (Scheme 4.4c). Activation of the thioglycoside with methyl triflate gave a P-mannoside as the only anomer. This approach was employed for the synthesis of the core pentasaccharide of N-linked glycoproteins. 

Yoshimura has introduced the p-methoxybenzyl group for N-protection in piperazine-2,5-diones (83CL1001 85BCJ1413). The N-alkylation is carried out with sodium hydride and p-methoxybenzyl bromide in DMF at room temperature. Deprotection is achieved by ceric ammonium nitrate (CAN) in acetonitrile-water. 

Deprotection of peptides. In a synthesis of bovine pancreatic ribonucleasc, the 33 protective groups required were removed by three treatments with l M TEMSA thioanisole at 0° for 60 minutes. The groups were Cbz, r-butyl, p-methoxybenzyl, and p-methoxybenzenesulfonyl. The final step involved air oxidation of the cysteine residues to disulfides mediated by glutathione.2... 

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