N-protected Α-amino Aldehydes Research Articles

Synthesis of enantioenriched 1,2-trans-diamines using the borono-Mannich reaction with N-protected α-amino aldehydes.

The three-component Petasis borono-Mannich reaction starting with easily accessible N-protected α-amino aldehydes produces efficiently and diastereoselectively 1,2-trans-diamines with an enantiomeric excess of up to 98%.

Rearrangement of N-tert-Butanesulfinyl α-Halo Imines with Alkoxides to N-tert-Butanesulfinyl 2-Amino Acetals as Precursors of N-Protected and N-Unprotected α-Amino Carbonyl Compounds

Reaction of N-tert-butanesulfinyl α-halo imines with alkoxides afforded new N-tert-butanesulfinyl 2-amino acetals in good to excellent yield. These N-tert-butanesulfinyl 2-amino acetals are convenient precursors for the TMSOTf-promoted synthesis of the corresponding N-protected α-amino aldehydes and ketones, as well as for the HCl-promoted synthesis of 2-amino acetal hydrochlorides and α-amino ketone and α-amino aldehyde hydrochlorides in high yield. Via this method, an asymmetric synthesis of (S)-cathinone hydrochloride (er 94:6) was achieved.

Influence of reaction conditions on products of the Pictet–Spengler condensation

The Pictet–Spengler reaction with N-protected α-amino aldehydes was found to be very sensitive to reaction conditions. The outcome of the reaction can be controlled mainly by choice of solvent. Tetrahydro-β-carbolines were obtained in apolar solvents, while in polar media octahydro-bipyrroloindoles were the main compounds. Temperature, amount of acid and reaction time also influenced the final results of the PS reaction. Depending on conditions, products with opposite configuration of stereogenic centre, descended from amino aldehydes, were formed as byproducts.

ChemInform Abstract: Asymmetric Synthesis of Monocyclic β-Lactams: Application of Imines Derived from Chiral N-Protected α-Amino Aldehydes in the Staudinger Reaction.

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ChemInform Abstract: Synthesis of N-Protected α-Amino Aldehydes from Their Morpholine Amide Derivatives.

Abstract A new method for the synthesis of N -protected α-amino aldehydes was developed. N -Protected α-amino amides of morpholine were easily prepared and then reduced with LiAlH 4 to produce clean N -protected α-amino aldehydes. This new scheme of synthesis can be used with Boc, Z and Fmoc amino-protecting groups.

ChemInform Abstract: Synthesis of Highly Epimerizable N-Protected α-Amino Aldehydes of High Enantiomeric Excess.

Abstract The Dess–Martin periodinane was found to be a superior oxidant for the efficient, epimerization-free synthesis of optically active N -protected α-amino aldehydes from the corresponding N -protected β-amino alcohols. Highly racemization-prone products, including N -Fmoc phenylglycinal and N -trifluoroacetyl α-amino aldehydes, were prepared in ≥95% yield with ≤1% epimerization.

Synthesis of diastereomerically pure 1,4,5-substituted-2-oxopiperazines on solid-phase

The first studies toward the solid-phase synthesis of 1,4,5-substituted-2-oxopiperazines are reported. The synthetic strategy is based on reductive alkylation of resin-bound amino acids using N-protected α-amino aldehydes (with concomitant epimerization), followed by acylation with α-chloroacetyl chloride. Subsequent stereoselective on-bead intramolecular cyclization has led to a diastereomerically pure 2-oxopiperazine.

Synthesis of 2,5-Disubstituted Pyrroles and Pyrrolidines by Intramolecular Cyclization of 6-Amino-3-keto Sulfones

Wittig reaction of 4-[(4-methylphenyl)sulfonyl]-1-(triphenylphosphoranylidene)butan-2-one (1) with N-protected α-amino aldehydes furnished N-protected γ-amino-α,β-unsaturated keto sulfones which have been conveniently utilized as precursors of both aromatic and non-aromatic 2,5-disubstituted five-membered heterocyclic compounds. While 2,5-disubstituted pyrroles are efficiently formed by cyclodehydration of the starting materials, 2,5-disubstituted pyrrolidines and pyrrolenines could be obtained by prior reduction of the conjugated double bond followed by acid- or base-mediated cyclization. The ready availability of the materials required for the whole sequence makes this methodology a convenient way to generate both aromatic and saturated 2,5-disubstituted five-membered heterocyclic compounds.

A short and efficient synthesis of N-Cbz-galantinic acid under promoter control on enantioselective acyclic stereoselection based on chiral oxazaborolidinone-promoted aldol reactions

An effective ‘promoter control’ on enantioselective acyclic stereoselection based on chiral oxazaborolidinone-promoted asymmetric aldol reactions has been found in the case of chiral N-protected α-amino aldehydes. An enantioselective synthesis of the title compound has been efficiently accomplished by using a sequence of the aldol reaction.

Synthesis of highly epimerizable N-protected α-amino aldehydes of high enantiomeric excess

The Dess–Martin periodinane was found to be a superior oxidant for the efficient, epimerization-free synthesis of optically active N-protected α-amino aldehydes from the corresponding N-protected β-amino alcohols. Highly racemization-prone products, including N-Fmoc phenylglycinal and N-trifluoroacetyl α-amino aldehydes, were prepared in ≥95% yield with ≤1% epimerization.

Synthesis of N-protected α-amino aldehydes from their morpholine amide derivatives

A new method for the synthesis of N-protected α-amino aldehydes was developed. N-Protected α-amino amides of morpholine were easily prepared and then reduced with LiAlH 4 to produce clean N-protected α-amino aldehydes. This new scheme of synthesis can be used with Boc, Z and Fmoc amino-protecting groups.

Cyclopropenone-containing cysteine proteinase inhibitors. Synthesis and enzyme inhibitory activities

By focusing on the amphiphilic properties of cyclopropenone (e.g. a good electrophile and a precursor for a stable 2π-aromatic hydroxycyclopropenium cation), a new class of cysteine proteinase inhibitors containing a cyclopropenone moiety was designed. For the purpose of the present research, we needed to devise a new method to introduce a peptide-related moiety as a substituent on the cyclopropenone residue. We investigated the reaction of metalated cyclopropenone acetal derivatives ( 2, R 2=metal) with N-protected α-aminoaldehydes 4 to obtain the adduct 5, and succeeded in the preparation of highly potentiated cysteine proteinase inhibitors 8 after several steps transformations. They showed strong inhibitory activities only to cysteine proteinases such as calpain, papain, cathepsin B, and cathepsin L and not to serine (e.g. thrombin and cathepsin G) and asparatic protainases (e.g. cathepsin D). Kinetic studies indicated that they are competitive inhibitors, and by the examinations of their inhibitory mechanism it became clear that they are reversible inhibitors. ©

A New Approach to 5-Hydroxyindoles from 1,4-Cyclohexanedione

Abstract Several kinds of 2-substituted 5-hydroxyindoles were prepared by the procedure starting from the condensation of 1,4-cyclohexanedione with N-protected α-amino aldehydes in the presence of lithium chloride. The substitutent on 2-position of the indole ring system depends on that of the α-amino acid which was converted to the aldehyde.

Preparation and Synthetic Applications of Sterically Hindered Secondary Amines

The preparation of sterically hindered secondary amino esters from the reaction of N-protected α-amino aldehydes and 3-, or 2-oxo esters with α-amino esters by reductive amination is described. The resulting amino esters were converted to the β-lactam or acylated to form N-acyl secondary amides.

Zinc-Mediated Allylation of N-Protected α-Amino Aldehydes in Aqueous Solution. Stereoselective Synthesis of Anti- and Syn-β-Amino Alcohols with Functionalized Allyl Groups

Zinc-Mediated Allylation of <i>N</i>-Protected α-Amino Aldehydes in Aqueous Solution. Stereoselective Synthesis of <i>Anti</i>- and <i>Syn</i>-β-Amino Alcohols with Functionalized Allyl Groups

CrCl 2 Mediated addition of allylic halides or phosphates to N-protected α-amino aldehydes. Stereocontrolled synthesis of a new core for C 2 symmetric HIV-protease inhibitors

The addition of γ-monosubstituted allylchromium(III) reagents to N-protected α-amino aldehydes proceeds in a stereoconvergent manner in contrast with the case of the unsubstituted reagents, where the stereoselectivity depends on the nature of the group bonded to the nitrogen. The chromium(III) reagent derived from 3-chloromethyl-2-trimethylsilyl-1-propene was used to prepare a C 2 symmetric HIV-protease inhibitor.

An Efficient Method for Preparation of Optically Active N-Protected α-Amino Aldehydes from N-Protected α-Amino Alcohols

N-Protected α-amino aldehydes of high optical purity were prepared in excellent yields from corresponding α-amino alcohols by 1,1,1-tris(acetoxy)-1,1-dihydro-1,2-benzoidoxol-3(H)-one (periodinane) oxidation.

Synthesis of chiral N-protected α-amino aldehydes by reduction of N-protected N-carboxyanhydrides (UNCAs)

A facile one step synthesis of a wide variety of N-protected (Boc, Z, Fmoc) α-amino aldehydes under mild conditions is described. Pure N-protected (Boc, Z, Fmoc) α-amino aldehydes were obtained in high yields by reduction of N-protected (Z, Boc, Fmoc)-N-carboxyanhydrides (UNCAs) with equivalent amounts of lithium tris(tertbutoxy)aluminium hydride [LiAlH(O-t-Bu) 3] or lithium tris[(3-ethyl-3-pentyl)oxy]aluminium hydride (LTEPA) in THF as solvent. The reaction is simple, rapid and proceeds without detectable racemization.

CrCl 2 mediated allylation of N-protected α-amino aldehydes. A versatile synthesis of polypeptides containing an hydroxyethylene isostere

Differently substituted allylic bromides react with N-protected amino aldehydes to give intermediate products for the synthesis of hydroxyethylene dipeptide isosteres. The low stereoselectivity of this reaction can be improved using aldehydes protected with hindered groups. This reaction can be efficiently applied to oligopetide aldehydes. We describe a protocol, for the preparation of peptides containing an hydroxyethylene isostere, which allows a rapid variations of the aminoacid sequence

Studies on the synthesis of cyanomethyleneamino pseudopeptides

Various cyanomethyleneamino pseudodipeptides were easily prepared in high yield by the Lewis acid catalyzed addition of trimethylsilyl cyanide to unstable aldimine intermediates, obtained from the reaction of N-protected α-amino aldehydes with C-protected amino acids. The two possible (R)- and (S)-epimers at the peptide bond surrogate chiral center were obtained. In this thermodynamically controlled synthesis, the absolute configurations of the α-amino aldehyde and the amino acid proved to be the main factors determining its stereoselectivity. The new N-Boc- and N-Z-protected pseudodipeptides were deblocked under standard conditions. In spite of the lability of the new peptide bond surrogate ψ[CH(CN)NH] in basic medium, high yields of C-deprotected pseudodipeptides were obtained by controlling the saponification conditions of the methyl esters. The use of free α-amino acids in the modified Srecker synthesis reported here can be employed as an alternative for the synthesis of C-deprotected cyanomethyleneamino pseudopeptides. The N- or C-elongation of these pseudodipeptides via the DCC method led to the corresponding ψ[CH(CN)NH] pseudotripeptides in high yields