Asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680. Issue 12 (15th December 2017)

• Record Type: Journal Article
• Authors: Davies, Stephen G.; Fletcher, Ai M.; Hanby, Abigail R.; Roberts, Paul M.; Thomson, James E.
• Is Part Of: Tetrahedron, asymmetry. Volume 28:Issue 12(2017)
• Page Start: 1756
• Page End: 1764
• Publication Date: 2017-12-15
• Subjects: Asymmetry (Chemistry) -- Periodicals; 547.005
• DOI: 10.1016/j.tetasy.2017.09.022
• Languages: English
• ISSNs: 0957-4166

Abstract

Graphical abstract: The asymmetric syntheses of the N-terminal syn -α-hydroxy-β-amino acid components of microginins 612, 646 and 680, and the corresponding C(2)-epimeric anti -α-hydroxy-β-amino acids, are reported using diastereoselective aminohydroxylation of the requisite ( E )-α, β-unsaturated esters as the key step. Abstract: The asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680 are reported. Conjugate addition of lithium ( R )- N -benzyl- N -(α-methylbenzyl)amide to the requisite ( E )-α, β-unsaturated ester followed by in situ enolate oxidation with (−)-(camphorsulfonyl)oxaziridne (CSO) gave the corresponding anti -α-hydroxy-β-amino esters. Sequential Swern oxidation followed by diastereoselective reduction gave the corresponding syn -α-hydroxy-β-amino esters. Subsequent N-debenzylation (i.e., hydrogenolysis for microginin 612, and NaBrO3 -mediated oxidative N-debenzylation for microginins 646 and 680) followed by acid catalysed ester hydrolysis gave the corresponding syn -α-hydroxy-β-amino acids, the N-terminal components of microginins 612, 646 and 680, in good yield. An analogous strategy for elaboration of the enantiopure anti -α-hydroxy-β-amino esters facilitated the asymmetric synthesis of the corresponding C(2)-epimeric α-hydroxy-β-amino acids. Abstract : tert -Butyl ( R, R, R )-2-hydroxy-3-[ N -benzyl- N -α-(methylbenzyl)amino]octanoate32 : C27 H39 NO3 [ α ]D 25 = −27.0 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: ( R, R, R ) Abstract : tert -Butyl ( R, R, R )-2-hydroxy-3-[ N -benzyl- N -α-(methylbenzyl)amino]-8-chlorooctanoate33 : C27 H38 ClNO3 [ α ]D 25 = −23.7 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: ( R, R, R ) Abstract : tert -Butyl ( R, R, R )-2-hydroxy-3-[ N -benzyl- N -α-(methylbenzyl)amino]-8, 8-dichlorooctanoate34 : C27 H37 Cl2 NO3 [ α ]D 25 = −19.0 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: ( R, R, R ) Abstract : tert -Butyl (2 S, 3 R, α R )-2-hydroxy-3-[ N -benzyl- N -α-(methylbenzyl)amino]octanoate38 : C27 H39 NO3 [ α ]D 25 = −24.4 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: (2 S, 3 R, α R ) Abstract : tert -Butyl (2 S, 3 R, α R )-2-hydroxy-3-[ N -benzyl- N -α-(methylbenzyl)amino]-8-chlorooctanoate39 : C27 H38 ClNO3 [ α ]D 25 = −20.8 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: (2 S, 3 R, α R ) Abstract : tert -Butyl (2 S, 3 R, α R )-2-hydroxy-3-[ N -benzyl- N -α-(methylbenzyl)amino]-8, 8-dichlorooctanoate40 : C27 H37 Cl2 NO3 [ α ]D 25 = −15.0 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: (2 S, 3 R, α R ) Abstract : tert -Butyl ( R, R )-2-hydroxy-3-aminooctanoate41 : C12 H25 NO3 [ α ]D 25 = +8.3 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: ( R, R ) Abstract : ( R, R )-2-Hydroxy-3-aminooctanoic acid19 : C8 H17 NO3 [ α ]D 25 = +3.6 ( c 1.0, MeOH) Source of chirality: Asymmetric synthesis Absolute configuration: ( R, R ) Abstract : tert -Butyl (2 S, 3 R )-2-hydroxy-3-aminooctanoate42 : C12 H25 NO3 [ α ]D 25 = −11.0 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: (2 S, 3 R ) Abstract : (2 S, 3 R )-2-Hydroxy-3-aminooctanoic acid16 : C8 H17 NO3 [ α ]D 25 = −6.0 ( c 1.0, H2 O/MeOH v/v 1:1) Source of chirality: Asymmetric synthesis Absolute configuration: (2 S, 3 R ) Abstract : tert -Butyl ( R, R, R )-2-acetoxy-3-[ N -benzyl- N -α-(methylbenzyl)amino]-8-chlorooctanoate43 : C29 H40 ClNO4 [ α ]D 25 = +1.8 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: ( R, R, R ) Abstract : tert -Butyl ( R, R )-2-hydroxy-3-acetamido-8-chlorooctanoate45 : C14 H26 ClNO4 [ α ]D 25 = −3.2 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: ( R, R ) Abstract : ( R, R )-2-Hydroxy-3-amino-8-chlorooctanoic acid20 : C8 H16 ClNO3 [ α ]D 25 = +20.4 ( c 1.0, MeOH) Source of chirality: Asymmetric synthesis Absolute configuration: ( R, R ) Abstract : tert -Butyl (2 S, 3 R, α R )-2-acetoxy-3-[ N -benzyl- N -α-(methylbenzyl)amino]-8-chlorooctanoate46 : C29 H40 ClNO4 [ α ]D 25 = +1.1 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: (2 S, 3 R, α R ) Abstract : (2 S, 3 R )-2-Hydroxy-3-amino-8-chlorooctanoic acid17 : C8 H16 ClNO3 [ α ]D 25 = −4.9 ( c 0.5, MeOH) Source of chirality: Asymmetric synthesis Absolute configuration: (2 S, 3 R ) Abstract : tert -Butyl ( R, R, R )-2-acetoxy-3-[ N -benzyl- N -α-(methylbenzyl)amino]-8, 8-dichlorooctanoate48 : C29 H39 Cl2 NO4 [ α ]D 25 = −1.8 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: ( R, R, R ) Abstract : ( R, R )-2-Hydroxy-3-amino-8, 8-dichlorooctanoic acid21 : C8 H15 Cl2 NO3 [ α ]D 25 = +32.7 ( c 0.5, MeOH) Source of chirality: Asymmetric synthesis Absolute configuration: ( R, R ) Abstract : tert -Butyl (2 S, 3 R, α R )-2-acetoxy-3-[ N -benzyl- N -α-(methylbenzyl)amino]-8, 8-dichlorooctanoate52 : C29 H39 Cl2 NO4 [ α ]D 25 = −1.5 ( c 1.0, CHCl3 ) Source of chirality: Asymmetric synthesis Absolute configuration: (2 S, 3 R, α R ) Abstract : (2 S, 3 R )-2-Hydroxy-3-amino-8, 8-dichlorooctanoic acid18 : C8 H15 Cl2 NO3 [ α ]D 25 = −7.7 ( c 0.5, MeOH) Source of chirality: Asymmetric synthesis Absolute configuration: (2 S, 3 R )