Asymmetric Syntheses of 3-Deoxy-3-aminosphingoid Bases: Approaches Based on Parallel Kinetic Resolution and Double Asymmetric Induction

Abstract

The asymmetric syntheses of a range of N- and O-protected 3-deoxy-3-aminosphingoid bases have been achieved using two complementary approaches. dl-Serine was converted to a racemic N,N-dibenzyl-protected γ-amino-α,β-unsaturated ester which was resolved using a parallel kinetic resolution (PKR) strategy upon reaction with a pseudoenantiomeric mixture of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide and lithium (S)-N-3,4-dimethoxybenzyl-N-(α-methylbenzyl)amide, giving the corresponding enantio- and diastereoisomerically pure β,γ-diamino esters. Alternatively, elaboration of l-serine gave the corresponding enantiopure N,N-dibenzyl-protected γ-amino-α,β-unsaturated ester, and doubly diastereoselective conjugate addition of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide was found to proceed under the dominant stereocontrol of the lithium amide reagent in both cases, thus augmenting the accessible range of β,γ-diamino esters. Both of these protocols were expanded to include in situ oxidation of the enolate formed upon conjugate addition, giving access to the corresponding α-hydroxy-β,γ-diamino esters. Elaboration of these β,γ-diamino and α-hydroxy-β,γ-diamino esters gave the protected forms of the 3-deoxy-3-aminosphingoid base targets.

Singlet Oxygen Photooxidation of Peptidic Oxazoles and Thiazoles

“…1 H NMR (400 MHz, D 2 O) δ 4.30 (t, 1 H, J = 3.7 Hz), 4.15–4.00 (m, 2H), 3.89 (s, 1H); 13 C­{ 1 H} NMR (100 MHz, D 2 O) δ 169.5, 59.8, 55.3, 54.3. Characterization data were consistent with previous literature …”

“…To a solution of L-serine (1070 mg, 10.2 mmol) in MeOH (15 mL) at 0 °C, SOCl 2 (4.3 mL, 59 mmol) was added dropwise over 15 min, and the mixture was then refluxed for 3 h. The mixture was concentrated under vacuum to give 11 as a yellow solid (1592 mg, 100%). 1 51 Synthesis of Methyl (tert-butoxycarbonyl)-L-valyl-L-serinate (12). A solution of Boc-val-OH (2.016 g, 9.3 mmol) and HOBt (190 mg, 1.4 mmol) in EtOH (45 mL) was stirred at room temperature for 15 min.…”