Synthesis of the 2,3-dihydro-6H-1,4-oxazin-2-ones chiral at C(3) and asymmetric induction in hydrogenation of the azomethine bond

Čaplar, Vesna; Lisini, A.; Kajfež, F.; Kolbah, D.; Šunjić, Vitomir

doi:10.1021/jo00401a015

Cited by 33 publications

(10 citation statements)

References 8 publications

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“…The morpholin-2-one templates required for the peptide synthesis can be prepared via synthetically complementary pathways. Routes described by Caplar and Sunjic [15] and Dellaria and Santarsiero [16] require access to the N-terminus protected amino acid or the amino alcohol; whereas two routes developed within our group permit access to (3S)-and (3R)-configured morpholinones which correspond to templated L and D amino acids respectively, not necessarily limited to the proteinogenic series [14,17,18]. In an initial study, the (3S,5R)-morpholinone template 1 was N-acetylated as a model for a C-terminus activated dipeptide and the adduct heated in DMSO-d 6 at 120 • C for 3 weeks (see supporting information).…”

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confidence: 99%

Morpholinone mediated oxazolone‐free C‐terminus amide coupling permitting a convergent strategy for peptide synthesis

Harwood

Mountford

Yan

2008

Journal of Peptide Science

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3-Substituted-5-phenylmorpholinones have been demonstrated to act as N-protected C-terminus activated alpha-amino acids capable of undergoing solution phase N-terminus peptide extension following standard coupling procedures. The N-acylated morpholinones do not undergo epimerisation of the stereocentre of the C-terminus amino acid residue as oxazolone formation is sterically prevented, although C-terminus peptide coupling is still possible. This convergent approach to peptide synthesis is exemplified by the preparation of L-ala-L-ala-L-ala and L-ala-D-ala-L-ala.

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confidence: 99%

Morpholinone mediated oxazolone‐free C‐terminus amide coupling permitting a convergent strategy for peptide synthesis

Harwood

Mountford

Yan

2008

Journal of Peptide Science

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“…Catalytic hydrogenation [20] of these derivatives under normal pressure in the presence of palladium on carbon allowed the isolation of the corresponding saturated cis-oxazinones 11 and 12 in 99 and 70% yield, respectively. No other diastereomers were detected ( 1 H NMR) and the relative stereochemistry was determined by NOE experiments, confirming that the hydrogenation of the imine moiety took place opposite to the bulky isopropyl group.…”

Section: Resultsmentioning

confidence: 99%

Asymmetric Synthesis of Substituted Prolines by 1,3-Dipolar Cycloadditions of Azomethine Ylides from Chiral 6-Isopropyl-5-phenylmorpholin-2-ones

et al. 2001

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“…The desired oxazinone 1 was obtained according to a modification of the procedure described by Sunjic et al, 12 which is outlined in Scheme 1. The starting material abromoisovalerophenone (3) was prepared by AlCl 3 -catalyzed bromination of the corresponding ketone following a standard method.…”

Section: Resultsmentioning

confidence: 99%

Chiral 3,6-Dihydro-2H-1,4-oxazin-2-ones as Alanine Equivalents for the Asymmetric Synthesis of α-Methyl α-Amino Acids (AMAAs) under Mild Reaction Conditions

Chinchílla¹,

Galindo²,

Nájera³

1999

Synthesis

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3,6-Dihydro-2H-1,4-oxazin-2-ones 1 act as very reactive chiral cyclic alanine equivalents and can be diastereoselectively alkylated or allylated using mild reaction conditions: potassium carbonate under phase-transfer catalysis (PTC) conditions when using activated alkyl halides, organic bases such as tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) when using unactivated alkyl halides, and neutral Pd(0)-catalysis when allylic carbonates are used. In most cases, the diastereoselectivity under all these different reaction conditions is excellent although the reactions are always carried out at room temperature. Hydrolysis of the obtained alkylated or allylated oxazinones allows the preparation of enantiomerically enriched (S)-a-methyl a-amino acids (S)-AMAAs. The PTC and organic base methodologies have also been applied to the synthesis of (R)-a-methyl a-amino acids starting from (R)-alanine. When dihalides are used as electrophiles under PTC or BEMP conditions, a spontaneous N-alkylation also takes place giving bicyclic oxazinones, which can be hydrolyzed to enantiomerically pure cyclic (S)-AMAAs.

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Synthesis of the 2,3-dihydro-6H-1,4-oxazin-2-ones chiral at C(3) and asymmetric induction in hydrogenation of the azomethine bond

Cited by 33 publications

References 8 publications

Morpholinone mediated oxazolone‐free C‐terminus amide coupling permitting a convergent strategy for peptide synthesis

Morpholinone mediated oxazolone‐free C‐terminus amide coupling permitting a convergent strategy for peptide synthesis

Asymmetric Synthesis of Substituted Prolines by 1,3-Dipolar Cycloadditions of Azomethine Ylides from Chiral 6-Isopropyl-5-phenylmorpholin-2-ones

Chiral 3,6-Dihydro-2H-1,4-oxazin-2-ones as Alanine Equivalents for the Asymmetric Synthesis of α-Methyl α-Amino Acids (AMAAs) under Mild Reaction Conditions

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