Synthesis of Fmoc-Protected Amino Alcohols via the Sharpless Asymmetric Aminohydroxylation Reaction Using FmocNHCl as the Nitrogen Source

Abstract

The aminohydroxylation of various alkenes using FmocNHCl as a nitrogen source is reported. In general, in the absence of a ligand, the reaction provided racemic Fmoc-protected amino alcohols with excellent regioselectivity but in low to moderate yields. However, in some instances, the yield of an amino alcohol product and the regioselectivity could be altered by the addition of a catalytic amount of triethylamine (TEA). The Sharpless asymmetric variant of this reaction (Sharpless asymmetric aminohydroxylation (SAAH)), using (DHQD)2PHAL (DHQD) or (DHQ)2PHAL (DHQ) as chiral ligands, proceeded more readily and in higher yield compared to the same reaction in the absence of a chiral ligand. The enantiomeric ratios (er) of all but two examples exceeded 90:10 with many examples giving er values of 95:5 or higher, making FmocNHCl a highly practical reagent for preparing chiral amino alcohols. The SAAH reaction using FmocNHCl was used for the preparation of d-threo-β-hydroxyasparagine and d-threo-β-methoxyaspartate, suitably protected for Fmoc solid phase peptide synthesis.

A54145 Factor D Is Not Less Susceptible to Inhibition by Lung Surfactant than Daptomycin

“…Fmoc- d - erythro -MeOAsp­( t -Bu)-OH was prepared using a route analogous to our previously disclosed routes (Scheme S1). − …”

“…Fmoc- d - threo -hAsn­(TBS)-OH was prepared using our procedure . A5D was prepared according to our procedure .…”

“…Fmoc-D-threo-hAsn(TBS)-OH was prepared using our procedure. 14 A5D was prepared according to our procedure. 13 Ent-A5D was prepared according to the same procedure but with the absolute configuration at each stereocenter inverted.…”

Solid-Phase Total Synthesis of Dehydrotryptophan-Bearing Cyclic Peptides Tunicyclin B, Sclerotide A, CDA3a, and CDA4a using a Protected β-Hydroxytryptophan Building Block

“…The route outlined in Scheme 3.10 was initially used and was based upon our synthesis of Fmoc-D-threo-HOAsn(Trt)-OH. 103,116 The route outlined in Scheme 3.13 was used for the large-scale synthesis of 3.9 which is based upon the procedures of Moeller et al 120 and Guzman-Martinez. 121 (50 mL), dried over MgSO4, evaporated and purified by FC (30 % EtOAc/70 % hexanes then 60 % EtOAc/38 % hexanes/2 % AcOH) to give 3.9 as an amorphous white solid (0.30 g, 60 % yield).…”

“…The next two residues, Fmoc-MeGlu­(O t Bu)-OH or Fmoc-Glu­(O t Bu)-OH, and Fmoc- d - e HOAsn­(Trt)-OH , were installed using DIC/HOBt to give peptides 17 and 18 . 2-Methylpiperidine (2-MP) was used to remove the Fmoc group to minimize the possibility of aminolysis of the ester bond.…”