Hydrogenation hydroxy-lactams

Another synthetic route to ( )-retronecine (27) has been developed by Vedejs and Martinez.11 The protected hydroxy-lactam (22) was prepared from 2-methoxy-1-pyrroline by known methods. The key ylide intermediate (24) was then generated from the salt (23) by desilylation with caesium fluoride (Scheme 6). This ylide (24) reacted with methyl acrylate in a 1,3-dipolar cycloaddition to afford the unsaturated pyrrolizidine (25) in 57% yield from the lactam (22). Catalytic hydrogenation of the ester (25) gave an unstable endo-product, which epimerized to the exo-form (26). Introduction of the 1,2-double-bond into (26) was carried out by insertion and thermal elimination of a phenylseleno-group.12 Reduction then yielded ( )-retronecine (27). 

Asymmetric [4+2j/[3+2]cycloadditions.2 The reaction of a chiral vinyl ether (2) and a nitroalkenc (1) catalyzed by a Lewis acid results in an intermediate adduct (a) which undergoes an intramolecular [3+2]cycloaddition. Both (+)-camphor and (—)-trans-2-phcnylhcxanol have been used as the chiral auxiliary. Thus the vinyl ether (2) formed from the latter auxiliary reacts with 1 to give 3 in 73% yield. Hydrogenation cleaves the chiral auxiliary and provides a tricyclic a-hydroxy lactam 4, in which... 

Sodium carbonatefsodium hydrogen carbonate )/-Hydroxy-> -lactams from cyanoketones... 

To complete the total S3mthesis of ent-staurosporine (2), a two-step deprotection strategy (hydrogenation followed by aminal hydrolysis) delivered 64 from 63 in high yield (Scheme 8). Danishefsky et al. preferred to clarify the monosaccharide domain prior to reducing the maleimide function [45], The most efficient method involved reduction of the imide group with sodium borohydride to provide a mixture of hydroxy lactams. Further reduction... 

The tautomeric properties of 5,6-dihydrocytosine and its alkyl derivatives have been studied by means of several spectroscopic methods (UV, IR, NMR) as well as by the pK evaluation.124,125 IR evidence shows that the tautomeric forms with a lactim hydroxy group at C-2 position are unimportant. On the other hand, NMR spectra show that structures of the lactam-amine type with two hydrogens at the C-6 position and with a hydrogen at the N-3 atom were also unimportant. 

The tautomeric ratio of 25 in water for 5,6-dihydrocytosine should be compared with the value of 105 for cytosine itself (see Table II). It thus appears that the hydrogenation of cytosine causes a substantial shift toward the imine form. A further shift toward the imine is observed when 5,6-dihydrocytosine is substituted at the amino group by a hydroxy group. It was shown124 by UV spectra that 1-alkyl-substituted A4-hydroxy-5,6-dihydrocytosines exist in aqueous solution in the lactam(ox)imine form 20. 

S-Hydroxy-l-azetidinones. A biomimetic synthesis of the y3-lactam 4 from BOC-L-serine (1) has been reported. The protected serine derivative is converted into the hydroxamic acid 2 by condensation with O-benzylhydroxylamine mediated by the water-soluble l-ethyl-3(3 -dimethylaminopropyl)carbodiimide (1, 371). The product is cyclized directly in high yield to the / -lactam 3 by treatment with diethyl azodicarboxylate and triphenylphosphine. No racemization is observed. Deprotection by catalytic hydrogenation gives the N-hydroxy-jS-lactam 4. Previous biomimetic syntheses of 2-azetidinones have involved cyclization ot /3-cMoroamides with sodium hydride (e.g., 7, 335). 

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