Highly Enantioselective Synthesis of Orthogonally Protected (2S)‐2,3‐Diaminopropanoates through Catalytic Phase‐Transfer Aza‐Henry Reaction

Abstract

The syntheses of enantiomer-enriched orthogonally protected different (2S)-2,3-diaminopropanoates and unnatural furyl-substituted (tert-butoxy)carbonyl (Boc) as well as (benzyloxy)carbonyl (Cbz) protected amino acid esters are accomplished by means of an enantioselective aza-Henry reaction. A key feature of this protocol is organocatalysis as a genesis of chirality to ensure high enantioselectivity.

The Stereoselective Nitro-Mannich Reaction in the Synthesis of Active Pharmaceutical Ingredients and Other Biologically Active Compounds

“…A few imino sugars have been synthesized in recent years by stereoselective nitro-Mannich reactions. In 2011 Kumaraswamy and Pitchaiah described a highly enantioselective synthesis of furyl-substituted (benzyloxy)carbonyl (Cbz) protected diamino acid esters through a catalytic phase-transfer aza-Henry reaction (Figure 4A; Kumaraswamy and Pitchaiah, 2011b). These protected nonproteinogenic α,β-diamino acids (DAPS), are of interest, since when incorporated into peptides, they can modulate their secondary and tertiary conformations; the peptides also become resistant to proteolysis (Viso et al, 2005;Arrayás and Carretero, 2009).…”

2,3-Diaminopropanols Obtained from d-Serine as Intermediates in the Synthesis of Protected 2,3-l-Diaminopropanoic Acid (l-Dap) Methyl Esters

“…Another critical step is the preservation of the absolute configuration of chiral carbon atoms when molecules from the natural chiral pool might be used as enantiomerically pure starting materials. Differently N α ,N β -diprotected l-Dap, as well as its mono-and di-alkylated derivatives, was obtained through a plethora of synthetic approaches [41][42][43][44][45][46][47][48][49][50][51][52]. In general, the published methods are characterized by variable overall yields in l-Dap, and they are notable for needing several steps of chromatography and for the problematic stereochemical control of reactions.…”

Peer Review #2 of "One-pot multicomponent nitro-Mannich reaction using a heterogeneous catalyst under solvent-free conditions (v0.1)"

“…The nitro functional group can also form other functionalities such as hydroxylamines [9], and oximes, or nitriles [10]. Indeed several natural products and pharmaceuticals have been synthesised via an intermediate nitro-Mannich reaction including antiemetic [11], analgesics [12], antimalarial and antiinsecticidal [13], antipsychotic [14,15], antiviral [16], anticancer [17,18], anti-HIV [19], antiparasitic [20], antidepressant [21], antibacterial and antimicrobial [22], and anaesthetic [23].…”