98818-41-8

Upstream product

• 591-51-5 phenyllithium 
• 104293-40-5 (5S,1'S)-5-<1-<<(tert-butyloxy)carbonyl>amino>-2-phenylethyl>-3-methylenedihydrofuran-2(4H)-one 
• 133333-27-4 tert-butyl (1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamate 
• 620-05-3 iodomethylbenzene 
• 499213-76-2 ((1S,2S,4R)-1-Benzyl-2-hydroxy-4-hydroxymethyl-5-phenyl-pentyl)-carbamic acid tert-butyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 145655-09-0 (3R,5S,1'S)-3-Benzyl-5-<1'--2'-phenylethyl>dihydrofuran-2(3H)-one 
• 98818-42-9 (3S,5S)-3-benzyl-5-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-phenylethyl}dihydrofuran-2-(3H)-one 
• 123054-12-6 (2S)-N,N-dibenzylphenylalaninal 
• 145655-01-2 (1'R,2'S)-2-<2-(N-benzyl-N-tert-butoxycarbonylamino)-1-hydroxy-3-phenylpropyl>-1,3-thiazole 
• 145655-02-3 (2R,3S)-3--2-<(tert-butyldimethylsilyl)oxy>-4-phenylbutanal 
• 145655-08-9 (3R,5S,1'S)-3-Benzyl-5-<1'--2'-phenylethyl>dihydrofuran-2(3H)-one 
• 145655-06-7 Methyl (4S,5S)-5--4-<(tert-butyldimethylsilyl)oxy>-6-phenylhexanoate 
• 145655-11-4 Methyl (4S,5S)-5--4-<(tert-butyldimethylsilyl)oxy>-6-phenyl-2(E)-hexenoate 

Downstream Products

• 132565-15-2 ((1S,2S,4R)-1-Benzyl-2-hydroxy-4-phenethylcarbamoyl-5-phenyl-pentyl)-carbamic acid tert-butyl ester 
• 132565-16-3 [(1S,2S,4R)-1-Benzyl-2-hydroxy-4-(indan-2-ylcarbamoyl)-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 98818-45-2 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid 
• 161916-90-1 (3R,5S)-5-((S)-1-Amino-2-phenyl-ethyl)-3-benzyl-dihydro-furan-2-one 
• 132565-32-3 [(1S,2S,4R)-1-Benzyl-2-hydroxy-4-(3-methyl-butylcarbamoyl)-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 126409-30-1 [(1S,2S,4R)-1-Benzyl-4-((S)-1-carbamoyl-3-methyl-butylcarbamoyl)-2-hydroxy-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 129252-92-2 (2R,4S,5S)-5-Amino-2-benzyl-4-hydroxy-6-phenyl-hexanoic acid [(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-3-methyl-butyl]-amide 
• 126409-66-3 {(1S,2S,4R)-1-Benzyl-4-[(S)-1-(2,3-dihydroxy-propylcarbamoyl)-2-methyl-butylcarbamoyl]-2-hydroxy-5-phenyl-pentyl}-carbamic acid tert-butyl ester 
• 126409-47-0 [(1S,2S,4R)-1-Benzyl-4-((S)-1-benzylcarbamoyl-2-methyl-butylcarbamoyl)-2-hydroxy-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 98818-68-9 [(1S,2S,4R)-1-Benzyl-4-((S)-1-benzylcarbamoyl-3-methyl-butylcarbamoyl)-2-hydroxy-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 132565-31-2 [(1S,2S,4R)-1-Benzyl-2-hydroxy-4-((S)-3-methyl-1-phenethylcarbamoyl-butylcarbamoyl)-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 129252-98-8 [(1S,2S,4R)-1-Benzyl-4-((S)-1-benzylcarbamoyl-2-methyl-butylcarbamoyl)-2-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 98818-75-8 [(1S,2S,4R)-1-Benzyl-4-((S)-1-benzylcarbamoyl-3-methyl-butylcarbamoyl)-2-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 126409-81-2 N'-(2-benzimidazolylmethyl)-N-<5(S)-<(tert-butoxycarbonyl)amino>-4(S)-hydroxy-6-phenyl-2(R)-(phenylmethyl)hexanoyl>isoleucine amide 

Relevant academic research and scientific papers

Design and synthesis of HIV-1 protease inhibitors for a long-acting injectable drug application

The design and synthesis of novel HIV-1 protease inhibitors (PIs) (1-22), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was initiated from compound 1, a Phe-Phe hydroxyethylene peptidomimetic PI, and was directed towards the discovery of new PIs suitable for a long-acting (LA) injectable drug application. Introducing a heterocyclic 6-methoxy-3-pyridinyl or a 6-(dimethylamino)-3-pyridinyl moiety (R3) at the para-position of the P1′ benzyl fragment generated compounds with antiviral potency in the low single digit nanomolar range. Halogenation or alkylation of the metabolic hot spots on the various aromatic rings resulted in PIs with high stability against degradation in human liver microsomes and low plasma clearance in rats. Replacing the chromanolamine moiety (R1) in the P2 protease binding site by a cyclopentanolamine or a cyclohexanolamine derivative provided a series of high clearance PIs (16-22) with EC50s on wild-type HIV-1 in the range of 0.8-1.8 nM. PIs 18 and 22, formulated as nanosuspensions, showed gradual but sustained and complete release from the injection site over two months in rats, and were therefore identified as interesting candidates for a LA injectable drug application for treating HIV/AIDS.

Application of the asymmetric aminohydroxylation reaction for the syntheses of HIV-protease inhibitor, hydroxyethylene dipeptide isostere and γ-amino acid derivative

An enantioselective synthesis of lactone 1, a precursor to the (2R,4S,5S) hydroxyethylene dipeptide isostere and amino acid AHPPA 2 has been accomplished from the common intermediate 5 employing Sharpless asymmetric aminohydroxylation as the key step.

Potent small molecule CCR1 antagonists

The present manuscript details structure-activity relationship studies of lead structure 1, which led to the discovery of CCR1 antagonists >100-fold more potent than 1.

Allyltrichlorostannane additions to α-amino aldehydes: Application to the total synthesis of the aspartyl protease inhibitors L-682,679, L-684,414, L-685,434, and L-685,458

The hydroxyethylene dipeptide isosteres L-682,679, L-684,414, L-685,434, and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-amino aldehyde, followed by hydroboration of the corresponding 1,2-

Short total synthesis of aspartyl protease inhibitors L-685,434, L-682,679 and L-685,458

Hydroxyethylene dipeptide isosteres L-685,434, L-682,679 and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-aminoaldehyde followed by hydroboration of the corresponding 1,2-syn and 1,2-anti a

Transition-state mimetics for HIV protease inhibitors: Stereocontrolled synthesis of hydroxyethylene and hydroxyethylamine isosteres by ester- derived titanium enolate syn and anti-aldol reactions

Stereocontrolled syntheses of hydroxyethylene dipeptide isostere and aminoalkyl epoxides for hydroxyethylamine isosteres are described. The stereochemistry of both stereogenic centers of the aminoalkyl epoxides 10 and 15 as well as they γ-lactone 17 was assembled by our recently developed highly selective ester-derived titanium enolate aldol reactions. The Ti- enolate of 6 reacted with (benzyloxy)acetaldehyde and cinnamaldehyde to provide the syn-aldol product 7 and anti-aldol product 12, respectively. Removal of the chiral template followed by Curtius rearrangement of the resulting acid provided the desired amine functionality. The present syntheses represent practical and enantioselective entry to a range of other dipeptide isosteres, which are not limited to amino acid derived substituents.

Ring-closing metathesis strategy to unsaturated γ- and δ-lactones: Synthesis of hydroxyethylene isostere for protease inhibitors

Ring-closing olefin metathesis of acrylates derived from allylic and homo allylic alcohols in the presence of the Grubbs' catalyst (10-15 mol%) and titanium isopropoxide (0.3-3 equiv) provided ready access to α, β- unsaturated γ and δ-lactones and an important dipeptide isostere intermediate.

Peptide inhibitors of aspartic proteinases with hydroxyethylene isostere replacement of peptide bond. I. Preparation of four diastereoisomeric (2R or 2S, 4R or 4S, 5S)-2-benzyl-5-[(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenylhexanoic acids

By two separate routes were prepared four diastereoisomers of (2R or 2S,5R or 5S)-3-benzyl-5-{(1S)-[(tert-butoxycarbonyl)amino]-2-phenylethyl}tetrahydrofuran- 2-ones (11, 12, 17 and 18). Since the furanones were derived from (S)-phenylalanine, absolute co

Zinc-Mediated Allylation of N-Protected α-Amino Aldehydes in Aqueous Solution. Stereoselective Synthesis of Phe-Phe Hydroxyethylene Dipeptide Isosteres

An efficient route for the synthesis of a Phe-Phe hydroxyethylene dipeptide isostere utilized for the design of potential inhibitors of renin and HIV-protease was developed.

5-amino-4-hydroxyhexanoic acid derivatives

Compounds of formula I STR1 or their hydroxy-protected derivatives, and compounds of formula I' STR2 wherein T is an acyl radical of formula Z STR3 wherein Rz is unsubstituted or substituted hydrocarbyl wherein at least one carbon atom has been replaced by a hetero atom with the proviso that a hetero atom is not bonded directly to the carbonyl to which the radical Rz is bonded, alkyl having two or more carbon atoms, lower alkenyl, lower alkynyl, aryl or unsubstituted or substituted amino, and wherein the radicals R1, B1, R2, R3, A1, A2 and NR4 R5 are as defined in the description, and precursors thereof, are described. The compounds have pharmaceutical activity, for example in the treatment of retroviral diseases, such as AIDS.