Starting from natural aspartic acid (6) a practical method for the synthesis of enantiomerically pure 3-amino alcohols 8 including 3,4-diamino derivatives is described. After perbenzylation of 6 and reduction of both carboxylates, position 4 of the resultant (dibenzylamino)butanediol ( 11) could be regioselectively blocked to afford the silyloxy-protected intermediate 12a. Functionalization of position 1 was accomplished by nucleophilic displacement reactions including a 2-fold migration of the dibenzylamino substituent or by reductive amination of the amino aldehyde 15. Both routes proceeded under complete preservation of the optical purity. For envisioned SAR studies, we, furthermore, report on the application of this method to a chirospecific synthesis of epi-and diepislaframine (9a and 9b) as diastereomers of the highly bioactive indolizidine alkaloid slaframine (9c). Our first approach including reductive coupling of the chiral amino aldehyde 15 with 3-hydroxypyrrolidine failed when formation of a quaternary ammonium salt occurred, preventing the anticipated anionic cyclization. Therefore, we turned out attention to methodology developed by Wasserman. In fact, introduction of a 3-hydroxypyrrole-2-carboxylate fragment gave a cyclization precursor (30b) which could be successfully transformed into epi-and diepislaframine.
Amino acids
Amino acids U 0400Asymmetric Synthesis with 6-tert-Butyl-5-methoxy-6-methyl-3,6-dihydro-2H-1,4-oxazin-2-one as a New Chiral Glycine Equivalent: Preparation of Enantiomerically Pure α-Tertiary and α-Quaternary α-Amino Acids. -The synthetic utility of oxazinone (V) as key intermediate in the synthesis of enantiomerically pure α-amino acids is studied. Oxazinone is prepared from α-hydroxy acid (I), itself obtained in excellent optical purity by optical resolution using (R)-phenylalaninol. Monoalkylation, dialkylation and cyclopropanation reactions of oxazinone (V) proceed with excellent yields and diastereoselectivities. The cyclopropanation reaction with epichlorohydrin enantiomers (XII), however, does not proceed with the expected stereoselectivity and cannot be used to achieve all four possible diastereomers. Further functionalization of the cyclopropane side chain is studied. Hydrolysis conditions for the release of the corresponding α-amino acids from the oxazinones are optimized for each substrate. In contrast to a previously described oxazinone (XXIII), no side reactions due to additional functional groups are possible. -(KOCH, C.-J.; SIMONYIOVA, S.; PABEL, J.; KAERTNER, A.; POLBORN, K.; WANNER*, K. T.; Eur.
The chiral enamide (I) is converted into the iminium salt (III) which reacts with the silyl enol ethers (IV), yielding the diastereomeric amidoalkylation products (V) and (VI).
ChemInform Abstract Isomerization of the N-acyltetrahydropyridines (I) gives s-trans/s-cis-mixture of the enamides (II) which are converted into acyliminium ions upon treatment with HCl and TiCl4. These react with the nucleophilic silyl enol ether (III) to yield predominantly the (R)-adducts (IV).
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