Diastereoselective synthesis of furanose and pyranose substituted glycine and alanine derivatives via proline-catalyzed asymmetric α-amination of aldehydes

Petakamsetty, Ramu; Ansari, Anas; Ramapanicker, Ramesh

doi:10.1016/j.carres.2016.09.011

Cited by 4 publications

(2 citation statements)

References 61 publications

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“…1 H NMR (600 MHz, CDCl 3 ): δ 4.95 (s, 1H), 4.61 (d, J = 5.9 Hz, 1H), 4.54 (dd, J = 5.9, 1.0 Hz, 1H), 4.20−4.16 (m, 1H), 3.70− 3.67 (m, 2H), 3.36 (s, 3H), 1.76−1.59 (m, 4H), 1.48 (s, 3H), 1.32 (s, 3H). 13 3-((3aR,4R,6R,6aR 73 To a solution of alcohol S21 (400 mg, 1.72 mmol) in CH 2 Cl 2 (11.5 mL) at RT was added DMP (876 mg, 2.07 mmol, 1.2 equiv) in one portion. The resulting mixture was stirred at RT for 1 h before the addition of a 1:1 mixture of a Na 2 S 2 O 3 satd aq solution and a NaHCO 3 satd aq solution (10 mL).…”

Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

et al. 2019

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Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme responsible for the methylation of nicotinamide (NAM) using cofactor S-adenosylmethionine (SAM). NNMT overexpression has been linked to diabetes, obesity, and a variety of cancers. Successful development of potent and selective NNMT inhibitors could further reveal the role of NNMT in various diseases, potentially enabling new treatments for metabolic disorders and several cancers. In this work, structure-based rational design led to the development of potent and selective alkynyl bisubstrate inhibitors of NNMT. The reported nicotinamide-SAM conjugate (named NS1) features an alkyne as a key design element that closely mimics the linear, 180°transition state geometry found in the NNMT-catalyzed SAM → NAM methyl transfer reaction. NS1 was synthesized as a single enantiomer and diastereomer in 14 steps and found to be a high-affinity, subnanomolar NNMTinhibitor. An X-ray co-crystal structure and structure-activity relationship (SAR) study revealed the unique ability of an alkynyl linker to span the methyl transfer tunnel of NNMT with ideal shape complementarity.

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Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

et al. 2019

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“…cules, [32][33][34][35][36][37][38][39][40][41] we recently reported the synthesis of D-threosphinganine, L-erythro-sphinganine and (-)-spisulosine from an aldehyde derived from aspartic acid. 42 In the retrosynthetic analysis, it was anticipated that both bestatin and epibestatin could be synthesized from acid 9 using peptide coupling followed by deprotection of the Boc and MOM groups.…”

Section: Syn Openmentioning

confidence: 99%

Diastereoselective Synthesis of (–)-Bestatin, Epibestatin, Phebestin and (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic Acid from an Aldehyde Derived from d-Phenylalanine

Jain

2019

SynOpen

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A convenient and efficient method for the synthesis of (–)-bestatin, epibestatin, phebestin, and (3S,4R)-4-amino-3-hydroxy-5-phenylpentanoic acid is reported. The key step is a proline-catalyzed α-hydroxylation of an aldehyde derived from d-phenylalanine, which leads to incorporation of a hydroxyl group at the α-position of that aldehyde with good yield and very high diastereoselectivity. Bestatin and its diastereomer epibestatin are synthesized from the same starting material using the same sequence of reactions, except for proline as the catalyst. An O-MOM and Boc-protected amino acid, a common intermediate for bestatin, was coupled with a dipeptide, H-Val-Phe-OMe followed by global deprotection to yield phebestin. (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic acid was also synthesized in eight steps from the same starting material. The reported synthetic route offers a general method for the synthesis of such types of compounds and their analogues by changing the proline catalyst and/or the starting material from d- to l-phenylalanine.

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Enantioselective Synthesis of (R)‐Antofine and (R)‐Cryptopleurine

Ansari

Ramapanicker

2018

ChemistrySelect

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Enantioselective syntheses of (R)-antofine and (R)-cryptopleurine starting from a 3-phenanthrenylpropanal derivative are reported. Asymmetric α-amination of this aldehyde is carried out in the presence of D-proline, which constitutes the key step in the syntheses and resulted in the formation of the new stereogenic center with very high enantioselectivity (94% ee).The indolizidine and quinolizidine moieties in the target molecules are formed through Pictet-Spengler reaction. The current method is shorter and high yielding in comparison with a similar strategy used for the synthesis of these molecules using proline-catalyzed α-hydroxylation of the same aldehyde.

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Diastereoselective synthesis of furanose and pyranose substituted glycine and alanine derivatives via proline-catalyzed asymmetric α-amination of aldehydes

Cited by 4 publications

References 61 publications

High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

Diastereoselective Synthesis of (–)-Bestatin, Epibestatin, Phebestin and (3S,4R)-4-Amino-3-hydroxy-5-phenylpentanoic Acid from an Aldehyde Derived from d-Phenylalanine

Enantioselective Synthesis of (R)‐Antofine and (R)‐Cryptopleurine

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