(5S,6S)-4,5-Dimethyl-3-methyl­acryloyl-6-phenyl-1,3,4-oxadiazinan-2-one

The title compound, C15H18N2O3, is an example of an oxadiazinan-2-one with significant inter­action between the N3-acyl and N4-methyl groups. These steric inter­actions result in a large torsion angle between the two carbonyl groups, not present with acyl substituents with less steric demand

(5R,6S)-4-Isopropyl-5-methyl-6-phenyl-3-propanoyl-2H-1,3,4-oxadiazinan-2-one

The title compound, C16H22N2O3, was synthesized during the course of a study on (1R,2S)-norephedrine-derived 1,3,4-oxadiazinan-2-ones. The conformation adopted by the isopropyl group is pseudo-axial relative to the oxadiazinan core. The allylic strain contributes to this conformational arrangement

(5S,6R)-5-Methyl-6-phenyl-4-propyl-1,3,4-oxadiazinane-2-thione

The title mol­ecule, C13H18N2OS, is an oxadiazinanthione derived from (1R,2S)-norephedrine. There are two molecules in the asymmetric. Both adopt roughly half-chair conformations; however, the 5-position carbon orients out of opposite faces of the oxadiazinanthiones plane in the two molecules. In the crystal structure, they are oriented as a dimer linked by a pair of N—H⋯S hydrogen bonds. The absolute configuration has been established from anomalous dispersion and confirms the known stereochemistry based on the synthetic procedure

Diastereoselective Synthesis of the HIV Protease Inhibitor Darunavir and Related Derivatives via a Titanium Tetrachloride-Mediated Asymmetric Glycolate Aldol Addition Reaction

Darunavir is a potent HIV protease inhibitor that has been established as an effective tool in the fight against the progression of HIV/AIDS in the global community. The successful application of this drug has spurred the development of derivatives wherein strategic regions (e.g., P1, P1’, P2, and P2’) of the darunavir framework have been structurally modified. An alternate route for the synthesis of darunavir and three related P1 and P1’ derivatives has been developed. This synthetic pathway involves the use of a Crimmins titanium tetrachloride-mediated oxazolidine-2-thione-guided asymmetric glycolate aldol addition reaction. The resultant aldol adduct introduces the P1 fragment of darunavir via an aldehyde. Transamidation with a selected amine (isobutylamine or 2-ethyl-1-butylamine) to cleave the auxiliary yields an amide wherein the P1’ component is introduced. From this stage, the amide is reduced to the corresponding β-amino alcohol and the substrate is then bis-nosylated to introduce the requisite p-nitrobenzenesulfonamide component and activate the secondary alcohol for nucleophilic substitution. Treatment with sodium azide yielded the desired azides, and the deprotection of the p-methoxyphenoxy group is achieved with the use of ceric ammonium nitrate. Finally, hydrogenation to reduce both the aniline and azide functionalities with concurrent acylation yields darunavir and its derivatives

(6R)-2-tert-Butyl-6-[(4R,5S)-3-isopropyl-4-methyl-5-phenyl­oxazolidin-2-yl]phenol

In the title compound, C23H31NO2, the lone pair on the nitro­gen atom is oriented to facilitate intra­molecular hydrogen bonding with the hydr­oxy group residing on the phenyl substituent. The five-membered ring adopts an envelope confornmation with the O atom at the flap. The absolute stereochemistry was verified by measurement of optical activity using a digital polarimeter

(6S)-2,4-Di-tert-butyl-6-[(4S,5R)-3-iso­propyl-4-methyl-5-phenyloxazolidin-2-yl]phenol

The title oxazolidine compound, C27H39NO2, was synthesized from N-isopropyl­norephedrine. The dihedral angle between the aromatic rings is 70.33 (5)°. The N atom of the heterocycle is oriented to allow intra­molecular O—H⋯N hydrogen bonding with the hydr­oxy substituent

(5S)-4-(2,2-Dimethyl­prop­yl)-5-isopropyl-1,3,4-oxadiazinan-2-one

The title compound, C11H22N2O2, has one chiral center and packs in the monoclinic space group P21. The asymmetric unit has five crystallographically independent mol­ecules, four of which engage in inter­molecular N—H⋯O hydrogen bonding

Crystal structure of 3-methyl-5-trimethylsilyl-1H-pyrazole

The title compound, C7H14N2Si, crystallizes in a tetragonal space group and exists as an N—H...N hydrogen-bonded tetramer, formed around the crystallographic fourfold rotoinversion axis. The molecular identity is clearly the 5-trimethylsilyl-3-methyl-1H-pyrazole tautomer and the structure is isomorphous with that of 5-tert-butyl-3-methyl-1H-pyrazole [Foces-Foces & Trofimenko (2001). Acta Cryst. E57, o32–o34]