60027-55-6

Upstream product

• 57224-63-2 methyl 2-(((benzyloxy)carbonyl)amino)-3-hydroxybutanoate 
• 57224-63-2 methyl (2S,3R)-2-(benzyloxycarbonylamino)-3-hydroxybutyrate 
• 2491-18-1 (S)-methyl 2-amino-4-(methylthio)butanoate hydrochloride 
• 501-53-1 benzyl chloroformate 
• 58861-76-0 5-Methyl-2-oxazolin-4-carbonsaeure-methylester 
• 1191124-96-5 N-benzyloxycarbonyl-α-(diphenylphosphono)glycine methyl ester 
• 75-07-0 acetaldehyde 
• 75266-39-6 methyl (S)-2-<<(benzyloxy)carbonyl>amino>-4-(methylsulfinyl)butanoate 
• 10332-17-9 Met-OMe 
• 1187361-27-8 benzyl (S)-1-(methoxycarbonyl)-3-(ethylsulfinyl)propylcarbamate 
• 1187361-40-5 benzyl (S)-1-(methoxycarbonyl)-3-(benzylsulfinyl)propylcarbamate 
• 1187361-42-7 benzyl (S)-1-(methoxycarbonyl)-3-(phenylsulfinyl)propylcarbamate 
• 1187361-44-9 benzyl (S)-1-(methoxycarbonyl)-3-(4-methoxyphenylsulfinyl)propylcarbamate 
• 1187361-43-8 benzyl (S)-1-(methoxycarbonyl)-3-(4-chlorophenylsulfinyl)propylcarbamate 

Downstream Products

• 61073-78-7 (Z)-methyl 2-(((benzyloxy)carbonyl)amino)-3-methylpent-2-enoate 

Relevant academic research and scientific papers

BABIPhos Family of Biaryl Dihydrobenzooxaphosphole Ligands for Asymmetric Hydrogenation

Novel bidentate phosphine ligands BABIPhos featuring a biaryl bis-dihydrobenzooxaphosphole core are presented. Their synthesis was achieved via Pd-catalyzed reductive homocoupling of dihydrobenzooxaphosphole aryl triflates. An efficient route toward various analogues was also established, giving access to phosphines with different electronic and steric properties. The newly obtained ligands demonstrated high efficiency and selectivity in Rh-catalyzed asymmetric hydrogenation of di- and trisubstituted enamides. This new class of ligands is complementary to previously described bidentate benzooxaphosphole ligands BIBOP.

The stereoselective construction of E- and Z-Δ-Ile from E-dehydroamino acid ester: the synthesis of the phomopsin A tripeptide side chain

The stereoselective synthesis of the phomopsin A tripeptide side chain was achieved by using methyl 2-(((benzyloxy)carbonyl)amino)-2-(diphenoxyphosphoryl)acetate as a common synthetic precursor for the synthesis of E-Δ-dehydroisoleucine and E-Δ-aspartate.

Continuous-flow thermolysis for the preparation of vinylglycine derivatives

Syn sulfoxide elimination was carried out under continuous-flow conditions in a mesofluidic thermolysis reactor. The design of the reactor enabled accurate control of reaction time and conditions, affording a convenient scale-independent procedure for the production of N,C-protected vinylglycine derivatives. Thermolysis at 270 °C under 1000 psi of pressure in superheated toluene enabled typical daily outputs ranging from 11 to 46 g per day with excellent selectivities and ee (>97%). The various competitive reaction pathways were studied and rationalized according to a computational study.

Stereoselective Synthesis of (E)-α,β-dehydroamino acid esters

Dehydroamino acid (Dhaa) is recognized as a useful tool or substrate for amino acid and peptide research. Although the stereoselective synthesis of the thermodynamically more stable Z-Dhaa has been well examined and established, the stereoselective synthesis of E-Dhaa has still remained to be a challenging synthetic task. In this paper, a stereoselective synthesis of E-Dhaa esters using a new (α-diphenylphosphono)glycine is described. The characteristic aspects of the new method are summarized as follows: (i) metal additives play an important role in the promotion of E-stereoselectivities. (ii) the use of NaI was effected for the synthesis of E-Dhaas bearing an aryl substituent and an amino functionality, (iii) MgBr2·OEt2 and ZnCl 2 contributed to improve the E-stereoselective synthesis of E-Dhaas bearing an alkyl substituent and an oxygen functionality, (iv) various protecting and functional groups were compatible under the reaction conditions, and (v) N-Cbz, Boc, and acyl-α-(diphenylphosphono)glycines were served for the stereoselective olefination reaction to provide the corresponding E-Dhaas. A variety of (E)-dehydroamino acid esters were stereoselectively synthesized by using (diphenylphosphono)glycinate. The stereoselectivity was influenced by metal additives. Various (E)-dehydroamino acid esters were prepared by the condensation reaction of the new phosphonates with easily available aldehydes by choosing the appropriate reaction conditions.

PREPARATION OF ALKENES BY MILD THERMOLYSIS OF SULFOXIDES

Embodiments of this disclosure, among others, encompass methods for generating alkenes under mild thermolytic conditions that can provide almost total conversion of a precursor compound to an alkene without isomerization or the need to chromatographically purify the final product By selectively blocking the amino and carboxy groups of the depvatized amino acid, the methods of the disclosure provide for the synthesis of a peptide having the vinylglycine moiety at either the carboxy or the amino terminus of the peptide The mild conditions for the thermolytic removal of an o-NO2-phenyl substituted aryl group ensure that there is minimal if any damage to thermally sensitive conjugates such as a peptide bearing the vinylglycine The methods of the present disclosure have practical applications for the preparation of unsaturated compounds under mild, thermolytic conditions.

An improved protocol for the preparation of (S)-vinylglycine from (S)-methionine

We present an optimized procedure for the synthesis of (S)-vinylglycine from (S)-methionine. The key step is a solvent free pyrolysis of an intermediate sulfoxide at high temperature. Using our optimized reaction conditions, Cbz-protected vinylglycine was

Preparation of vinylglycines by thermolysis of homocysteine sulfoxides

The synthesis and efficacy of preparing Cbz-VG-OMe (1) by thermolysis of alkyl and aryl homocysteine sulfoxides were surveyed. This investigation determined that aryl sulfoxide analogs were more effective for the reaction and that the 2-nitrophenyl analog 10f possessed a unique ability to syn eliminate at temperatures as low as 100 °C. The thermolysis of sulfoxide 10f was additionally discovered to occur under toluene reflux and when sodium acetate was added, Cbz-VG-OMe (1) could be obtained in high purity by simple filtration of the precipitated sulfenic acid byproduct 12. This mild protocol which was also applied in the synthesis of VG dipeptide 13 would have utility in the general synthesis of olefins and alkenes from 2-nitrophenylsulfoxides.

A stereoselective synthesis of phosphinic acid phosphapeptides corresponding to glutamyl-γ-glutamate and incorporation into potent inhibitors of folylpoly-γ-glutamyl synthetase

Radical addition of H3PO2 to N-/C-protected vinyl glycine led to the corresponding H-phosphinic acid in excellent yield. The non-nucleophilic H-phosphinic acid was converted to a nucleophilic P III species, RP(OTMS)2, which was used in two approaches to the target phosphinic acid containing pseudopeptide. New methodology was developed that led to excellent yields in the reaction of RP(OTMS)2 with unactivated electrophiles, including an acyclic homoallylic bromide. However, en route to the target pseudopeptide, Arbuzov reaction of RP(OTMS) 2 with a cyclic homoallylic bromide, (R)-3-(bromomethyl)-cyclopent-1- ene, led to a rearranged allylic phosphinic acid rather than the desired homoallylic derivative, a putative glutarate surrogate. Conjugate addition of RP(OTMS)2 to α-methylene glutarate containing a chiral auxiliary resulted in only modest diastereoselectivity. Purification by flash chromatography provided protected derivatives of both diastereomers of the pseudopeptide. Following global deprotection, coupling of (S)-H-Glu-γ- [Ψ(P(O)(OH)(CH2))]-(S)-Glu-OH and (S)-H-Glu-γ-[Ψ(P(O) (OH)(CH2))]-(R)-Glu-OH to (4-amino-4-deoxy-10-methyl)pteroyl azide led to the target compounds for biochemical study as inhibitors of the ATP-dependent ligase, folylpoly-γ-glutamate synthetase.

Enantioselective Synthesis of Non-Natural Aromatic α-Amino Acids

We present two complementary methods for the stereoselective synthesis of non-natural α-amino acids with aromatic or heteroaromatic side chains. One approach is based on the chemical transformation of methionine, whereas the other applies the stereoselective Myers alkylation of glycine. The resulting product types differ in the linker length between glycine and the aromatic substituent. Since methionine and pseudoephedrine are available in both absolute configurations, R- or S-configured enantiopure amino acids with either C2 or C3 linkers can be obtained on gram scales. In each case the key step of the synthesis is hydroboration of the unsaturated building blocks 9 and 17, followed by palladium-catalyzed Suzuki cross-coupling with aryl halides. Attention must in certain cases be paid to the stereochemical integrity when basic Suzuki conditions are applied. Our initial difficulties are reported as well as the final "racemization-proof" procedures. The protecting groups chosen for the α-amino acids should be compatible with solid-phase peptide synthesis. This was confirmed by the successful synthesis of a series of tripeptides.

Stereoselective syntheses of (E)-α,β-dehydroamino acids and (E)-α,β-dehydropeptides by stereospecific dehydration with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)

Highly stereoselective syntheses of (E)-α,β-dehydroamino acids and (E)-α,β-dehydropeptides have been achieved in good yields by stereospecific dehydration of threo-β-hydroxy-α-amino acid derivatives using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC