Asymmetric oxidation of ester and amide enolates using new (camphorylsulfonyl)oxaziridines

Abstract

recommend the procedures of Table I1 using allyloxycarbonyl chloride (AOCC1) or allyl l-benzotriazoylcarbonate (AOCOBT) (23): where choice of the base and solvent is important for obtaining satisfactory yields.The AOC group is also employable for the sugarhydroxyl p r o t e c t i~n .~,~ The 0-allyloxycarbonylated nucleoside 8 was prepared in 95% yield by tert-butylmagnesium chloride (2 equiv) aided reaction of cytidine nucleoside 13 (1 equiv) and the AOC agent 22 (1.2 equiv). When this 0-AOC nucleoside was treated with a catalytic amount of Pd[P(C6H5)3]4 in the presence of HCOOH/n-C4H,NH2 (2 equiv each) for 1 h, 13 was brought back. Conveniently, the Pd(0)-catalyzed reaction of the N,Obis(allyloxycarbony1ated) derivative 5 removed contemporaneously both protections to afford the nucleoside 7 in quantitative yield.Internucleotide linkage is protectable by allyl group.1° The above described characteristic properties of AOC, coupled with the phosphite method using allyl phosphorodichloridite, enabled us to open an extremely convenient way to dinucleoside phosphates. The key operation here is complete deprotection of fully-protected dinucleoside phosphotriester intermediates by single treatment with Pd(0) catalyst. Thus, collidine-assisted (4.6 equiv) condensation of the 3'-O-unprotected thymidine nucleoside 21 (2 equiv), CH2=CHCH20PC12 (2 equiv), and the 5'-0free adenosine 6 (1 equiv) followed by NO2 oxidation (THF, -78 "C) afforded the protected TpA 24 in 80% yield. When 24 was treated with a mixture of Pd[P(c6-)3]4 and P(C6H5)3 (5 and 20 mol %/allyl), formic acid (10 equiv), and butylamine (10 equiv) in THF at room temperature for 30 min, the four allylic protecting groups were removed all at once from the nucleoside base, sugar hydroxyl, and internucleotide bond to give TpA (25) in 97% yield. In summary, the AOC group acts as both specific and general protectors. This method is useful in view of mildness of the deprotection conditions and simplicity of the workup, providing a powerful tool in nucleotide synthesis. Supplementary Material Available: Experimental details(16 pages). Ordering information is given on any current masthead page.(7) We are grateful to Hodogaya Chemicals, Co., for the generous gift of allyloxycarbonyl chloride.(8) AOCOBT (23), mp 107-111 "C, was prepared by the triethylamine-promoted (1 equiv) reaction of AOCCl (22) (1 equiv) and 1hydroxybenzotriazole (1 equiv) in THF at room temperature for 10 min. (9) Guibe, F.; MLeux, Y. S. Tetrahedron Lett. 1981, 22, 3591. (IO) Hayakawa, Y.; Uchiyama, M.; Kato, H.; Noyori, R. Tetrahedron Lett. 1985, 26, 6505.Summary: The first asymmetric oxidation of ester and amide lithium enolates 5 to optically active a-hydroxy carbonyl compounds 6 is reported using new, easily prepared, stable (camphorylsulfony1)oxaziridines (+)-(2R,8&)-3 and (-)-(2S,8&)-4. Either enantiomer of 6 can be readily obtained because the configuration of the oxaziridine three-membered ring determines the product stereochemistry.Sir: Optically active a-hydroxy carbonyl compounds are ver...

Tumor suppressor gene RBM5 delivered by attenuated Salmonella inhibits lung adenocarcinoma through diverse apoptotic signaling pathways

“…This finding, although it needs to be validated by further experiments, strongly suggested that RBM5 could initiate TNF-α-mediated apoptosis [39], in which capase-8, caspase-3 and PARP were activated. This potential apoptosis pathway induced by RBM5 could also be observed in human breast carcinoma MCF-7 cells [40,41] and leukemia Jurkat cells [42]. The current data suggest that although RBM5’s involvement in the death receptor-mediated apoptotic pathway is still to be investigated in depth, RBM5-mediated growth suppression, at least in part, employs regulation of the mitochondrial apoptotic pathways.…”

Diastereoselective synthesis, binding affinity for vitamin D receptor, and chiral stationary phase chromatography of hydroxy analogs of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol

“…According to the current nomenclature, the systematic names of esters 5 and 6 are derived from C-24 cholanic acids 17 and hydroxylated compounds 1-4 and 9-16 from seco-cholestane. 28,29 The use of our previously developed 21 chiral stationary phase 30,31,32,33 HPLC (HPLC*) allowed us to determine the content of contaminating diastereomer of the opposite chirality (Figs. 85%).…”

“…This stereochemical outcome was consistent with the previously described stereochemistry of oxidation products of ␣and ␤-phenyl substituted carboxylic acid methyl esters. 28,29 The use of our previously developed 21 chiral stationary phase 30,31,32,33 HPLC (HPLC*) allowed us to determine the content of contaminating diastereomer of the opposite chirality ( Figs. 2 and 3).…”

Syntheses and Biological Activities of (2S,2′S)- and (2S,2′R)-Dimethyl 3-Phenyl-2,2′-oxydipropionate, Ether Analogues of a Plant-growth Regulator Isolated fromBotrytis squamosa

“…Five grams of ( ± )-methyl 2-bromopropionate (2) and 3.6 g of (S)-methyl 2-hydroxy-3-phenylpropionate (3) were dissolved in 26 ml of THF. After the solution had been cooled to -40C O.72g of sodium hydride was added.…”