182316-18-3

Upstream product

• 74879-45-1 C₁₆H₁₇NO₂ 
• 298-12-4 Glyoxilic acid 
• 321174-91-8 (S)-2-(hydroxyamino)-2-phenylethanol 
• 20989-17-7 (2S)-2-phenylglycinol 

Downstream Products

• 221284-61-3 (2S,3aS,7S)-2-Hydroxymethyl-7-phenyl-tetrahydro-isoxazolo[3,2-c][1,4]oxazin-4-one 
• 321174-81-6 (3aR,3bS,7S,8aS)-7-phenyl-3,3a,3b,6,7,8a-hexahydro-5,8-dioxa-7a-azacyclopenta[a]inden-4-one 
• 645396-53-8 (2S,5S,8aS)-2-(hydroxymethyl)-2-[(indol-3-yl)methyl]-5-phenyl-1,5,6,8a-tetrahydro-3,7-dioxaindolizin-8(2H)-one 
• 645396-54-9 (2S,5S,8aS)-2-[(1-(tertbutoxycarbonyl)indol-3-yl)methyl]-2-(hydroxymethyl)-5-phenyl-1,5,6,8a-tetrahydro-3,7-dioxaindolizin-8(2H)-one 
• 645396-60-7 (2S,5S,8aS)-2-[(tert-butyl(dimethyl)silyloxy)methyl]-2-[(1-(tert-butoxycarbonyl)indol-3-yl)methyl]-2-(hydroxymethyl)-5-phenyl-1,5,6,8a-tetrahydro-3,7-dioxaindolizin-8(2H)-one 
• 645396-59-4 (2S,5S,8aS)-2-[(tert-butyl(dimethyl)silyloxy)methyl]-2-[(indol-3-yl)methyl]-2-(hydroxymethyl)-5-phenyl-1,5,6,8a-tetrahydro-3,7-dioxaindolizin-8(2H)-one 

Relevant academic research and scientific papers

Route to Quaternary Oxaprolinol Derivatives as Masked Precursors of Disubstituted β3,β3-Amino Aldehyde

Bicyclic isoxazolidines displaying one or two quaternary stereocenter(s) were formed starting from functional cyclic ketonitrones equipped with a phenyl glycinol chiral auxiliary. The products were engaged in stereocontrolled 1,3-dipolar cycloaddition reactions with a range of electron-rich and electron-poor dipolarophiles. A new reductive removal of the phenyl glycinol chiral auxiliary was introduced and was shown to afford chemoselectively a quaternary isoxazolidine derivative (of oxaprolinol-type) without cleaving the N-O isoxazolidine bond. Keeping the aldehyde function masked as a cyclic pseudo-acetal, the liberated oxy-amine function was shown to be available for a pseudo-peptide coupling with various N-protected amino acids. The isoxazolidine ring was opened by a reductive N-O bond cleavage, giving a pseudo-dipeptide that was C-terminated with an aldehyde function. Isoxazolidines displaying a quaternary stereocenter were formed starting from functional cyclic ketonitrones through a highly stereocontrolled 1,3-dipolar cycloaddition. Chemoselective reductive chiral auxiliary removal gives quaternary oxaprolinol derivatives, which were further transformed into dipeptides terminated directly with an aldehyde function.

Design, synthesis, and 1,3-dipolar cycloaddition of (5R)- [and (5S)]-5,6-dihydro-5-phenyl-2H-1,4-oxazin-2-one N-oxides as chiral (E)-geometry-fixed α-alkoxycarbonylnitrones

Optically pure (5R)- [and (5S)]-5,6-dihydro-5-phenyl-2H-1,4-oxazin-2-one N-oxides [(5R)- and (5S)-2] were designed as chiral (E)-geometry-fixed α-alkoxycarbonylnitrones 1. The nitrones (5R)- and (5S)-2 were synthesized by three-step oxidation of (R)- and (S)-phenylglycinols [(R)- and (S)-3], condensation of the resulting (R)- and (S)-2-hydroxylamino-2-phenylethanols [(R)- and (S)-5] with glyoxylic acid, and cyclization of the intermediary nitrones (R)- and (S)-6b. The nitrone (5R)-2 reacted with olefins 7-14 under mild conditions to afford the corresponding cycloadducts 15-22 as the main products via the least sterically demanding exo modes. Cycloadduct 30 obtained from (5S)-2 and cyclopentadiene was effectively elaborated to (1S,4S,5R)-4-benzyloxycarbonylamino-2-oxabicyclo[3.3.0]oct-7-en-3-one (28), the key synthetic intermediate of carbocyclic polyoxin C.