- Stereospecific synthesis of oligonucleotides containing crotonaldehyde adducts of deoxyguanosine
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Crotonaldehyde reacts with DNA to form two diastereomeric 1,N2 cyclic adducts of deoxyguanosine. A synthesis of the two diastereomeric deoxynucleosides has been achieved by reaction of mixed diastereomers of 4-amino-1,2-pentanediol with 2-fluoro-O6-(trimethylsilylethyl)-deoxyinosine. The resulting N2-(1-methyl-3,4-dihydroxybutyl)-deoxyguanosine was treated with NaIO4, cleaving the vicinal diol to the aldehyde. Spontaneous cyclization gave the two diastereomers of the crotonaldehyde-adducted nucleoside that were readily separated by HPLC. The absolute configurations were assigned by an enantiospecific synthesis of one diastereomer from (S)-3-aminobutanoic acid. The synthetic strategy has been extended to preparation of a site-specifically adducted oligonucleotide by reaction of the mixed diastereomers of 4-amino-1,2-pentanediol with an 8-mer oligonucleotide containing 2-fluoro-O6-(trimethylsilylethyl)-deoxyinosine. The diastereomeric oligonucleotides were separated by HPLC and absolute configurations of the adducts were established by enzymatic digestion to the adducted nucleosides.
- Nechev,Kozekov,Harris,Harris
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p. 1506 - 1512
(2007/10/03)
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- Lewis Acid-Promoted 1,4-Addition to Chiral Imide Derivatives in the Synthesis of β-Amino Acids
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The 1,4-addition of O-benzylhydroxylamine to imides 3 in the presence of various Lewis acids is described.The reaction is performed in CH2Cl2 at -78 deg C and affords derivatives 4 and 5 in good chemical yields and in different diastereomeric ratios, depending on the Lewis acid employed.TiCl4 and Me2AlCl give opposite diastereoselectivities.Furthemore, enantiomerically pure β-amino acid 9 is obtained in good yield from compound 4a.
- Amoroso, Rosa,Cardillo, Giuliana,Sabatino, Piera,Tomasini, Claudia,Trere, Alessandra
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p. 5615 - 5619
(2007/10/02)
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- 194. Diastereoselecktive Alkylation of 3-Aminobutanoic Acid in the 2-Position
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The enantiomerically pure 3-aminobutanoic acids (R)- and (S)-6 are readily available by preparative HPLC separation of the two diastereoisomers 5 obtained from addition of (S)-phenethylamine to methyl crotonate and subsequent hydrogenolysis (Scheme 2). (S)-methyl 3-(benzoylamino)butanoate ((S)-3) is also available by enzymatic kinetic resolution with pig-liver esterase.The N-benzoyl- and N-benzyloxycarbonyl derivatives rac-3, 8,and 9 of 3-aminobutanoates are doubly deprotonated with LDA and alkylated or aminated in high selectivity (17 examples, relative topicity like; see Tables 1 and 2).The configuration of three of the products is assigned (Schemes 4-6), and in four cases, the free α-substituted β-amino acid is prepared by acidic hydrolysis (see Table 3).It is shown that the doubly lithiated β-amino-acid derivative is solubilized, and its reactivity may be strongly influenced by the presence of 3 equiv. of LiCl.
- Estermann, Heinrich,Seebach, Dieter
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p. 1824 - 1840
(2007/10/02)
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- Synthesis of β-Amino-acid Peptides. Part 3. Preparation of Racemic and Chiral 3-Aminobutyric Acid Derivatives and Peptides Using Dihydrooxazin-6-ones and Conventional Coupling Reagents
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Peptides of R,S and S-3-aminobutyric acid have been prepared by conventional methods and also by using chiral oxazin-6-ones, the latter method proving to be superior because of the absence of the side-reactions.S-3-Aminobutyric acid derivatives were prepared by Arndt-Eistert homologation.
- Drey, Charles N. C.,Mtetwa, Eli
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p. 1587 - 1592
(2007/10/02)
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- Selective Hydrogenation of 4,5-Dihydro-1,3-oxazin-6-ones to Carbaldehyde Derivatives; Chemical Differentiation between Acylazetidin-2-ones and the Corresponding Isomeric Oxazin-6-ones
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Catalytic hydrogenation of optically active and non-active dihydro-oxazin-6-ones unexpectedly led to preferential reduction of the carbonyl group with ring-opening yielding carbaldehyde derivatives.This reaction resolved a structural problem by leading to
- Drey, Charles N. C.,Ridge, Richard J.,Mtetwa, Eli
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p. 378 - 380
(2007/10/02)
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