153223-11-1

Upstream product

• 153181-25-0 (4R,5S,6S,7R)-hexahydro-5,6-bis(2-methoxyethoxymethoxy)-4,7-bis(phenylmethyl)-2H-1,3-diazepin-2-one 
• 58917-85-4 N-(benzyloxycarbonyl)-D-phenylalaninol 
• 63219-70-5 N-(benzyloxycarbonyl)-D-phenylalaninal 
• 183814-19-9 ((1S,2R,3S,4R)-1-Benzyl-4-benzyloxycarbonylamino-2,3-dihydroxy-5-phenyl-pentyl)-carbamic acid benzyl ester 
• 153223-10-0 (2R,3S,4S,5R)-2,5-bis[N-(benzyloxycarbonyl)amino]-1,6-diphenyl-3,4-hexanediol 
• 201230-82-2 carbon monoxide 
• 219586-75-1 (2R,3S,4S,5R)-2,5-diamino-1,6-diphenyl-3,4-hexanediol 

Downstream Products

• 170028-72-5 (3aS,4R,8R,8aS)-4,8-dibenzyl-2,2-dimethyltetrahydro-3aH-[1,3]dioxolo[4,5-e][1,3]diazepin-6(7H)-one 
• 151867-81-1 DMP 323 
• 179894-02-1 Acetic acid (4R,5S,6S,7R)-4,7-dibenzyl-6-hydroxy-2-oxo-[1,3]diazepan-5-yl ester 

Relevant academic research and scientific papers

Carbonylation of functionalized diamine diols to cyclic ureas: Application to derivatives of DMP 450

Synthesis of the cyclic urea core structure of the HIV protease inhibitor DMP 450 has been achieved via W(CO)6/I2-catalyzed carbonylation of diamine intermediates. Carbonylations of related functionalized diamines to derivatives of the DMP 450 core structure were also examined. Selected diamine diol substrates could be converted to the cyclic urea core structure by catalytic carbonylation without protection of the diol functionality.

Calculated and experimental low-energy conformations of cyclic urea HIV protease inhibitors

One important factor influencing the affinity of a flexible ligand for a receptor is the internal strain energy required to attain the bound conformation. Calculation of fully equilibrated ensembles of bound and free ligand and receptor conformations are computationally not possible for most systems of biological interest; therefore, the qualitative evaluation of a novel structure as a potential high- affinity ligand for a given receptor can benefit from taking into account both the bound and unbound (usually aqueous) low-energy geometries of the ligand and the difference in their internal energies. Although many techniques for computationally generating and evaluating the conformational preferences of small molecules are available, there are a limited number of studies of complex organics that compare calculated and experimentally observed conformations. To assess our ability to predict a priori favored conformations of cyclic HIV protease (HIV-1 PR) inhibitors, conformational minima for nine 4,7- bis(phenylmethyl)-2H-1,3-diazepin-2-ones I (cyclic ureas) were calculated using a high temperature quenched dynamics (QD) protocol. Single crystal X-ray and aqueous NMR structures of free cyclic ureas were obtained, and the calculated low-energy conformations compared with the experimentally observed structures. In each case the ring conformation observed experimentally is also found in the lowest energy structure of the QD analysis, although significantly different ring conformations are observed at only slightly higher energy. The 4- and 7-benzyl groups retain similar orientations in calculated and experimental structures, but torsion angles of substituents on the urea nitrogens differ in several cases. The data on experimental and calculated cyclic urea conformations and their binding affinities to HIV-1 PR are proposed as a useful dataset for assessing affinity prediction methods.

Stereoselective synthesis of HIV-1 protease inhibitor, DMP 323

DMP 323, a potent HIV-1 protease inhibitor, has been synthesized by an efficient stereoselective process, amenable to large scale preparations. The core C2 symmetric diol was synthesized by a stereoselective pinacol coupling of CBZ protected D-phenylalanine. Judicious selection of protecting groups allowed cyclic urea formation under mild conditions, enhanced the ease of bis-alkylation, and led te intermediates which were easily purified without chromatography. Additionally, a one-pot, high yield process was developed te prepare the alkylating agent, 4-[(triphenylmethoxy)methyl]benzyl chloride from 1,4-benzenedimethanol.

Cyclic HIV protease inhibitors: Synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas

High-resolution X-ray structures of the complexes of HIV-1 protease (HIV-1PR) with peptidomimetic inhibitors reveal the presence of a structural water molecule which is hydrogen bonded to both the mobile flaps of the enzyme and the two carbonyls flanking

A Practical Synthesis of Nonpeptide Cyclic Ureas as Potent HIV Protease Inhibitors

The utilization of the oxydimethylene group to form a trioxepane ring for the protection of 1,2-diols was demonstrated.A process starting with natural L-tartaric acid as the chiral building block is utilized in the synthesis of optically active, nonpeptid