Enantioselective synthesis of (2R,3R)- and (2S,3S)-β-hydroxyornithine

An efficient and short synthesis of (2R,3R)- and (2S,3S)-β-hydroxyornithine 1a-b is described using Sharpless asymmetric dihydroxylation and regioselective nucleophilic opening of a cyclic sulfite as the key steps.     

Synthesis of (E)- and (Z)-α,β-difluorourocanic acid

Horner-Emmons fluoroolefination of an aryl aldehyde followed by introduction of a second fluorine via “FBr” addition provides an original approach to the preparation of 1-alkyl-2-aryl-1,2-difluoroethenes. The utility of this procedure is demonstrated by the preparation of (E and Z)-α,β-difluorourocanic acid.     

The first asymmetric total synthesis of (R)-tuberolactone, (S)-jasmine lactone and (R)-δ-decalactone

A general synthetic approach has been developed for the first asymmetric total synthesis of tuberolactone 1, jasmine lactone 2 and δ-decalactone 3. The key step is the selective hydrogenation of triple and endocyclic double bonds in the key intermediate 4.     

Synthesis of β-chloro α-amino acids: (2S,3R)- and (2S,3S)-3-chloroleucine

The first syntheses of (2S,3R)- and (2S,3S)-3-chloroleucine (3-chloro-d-leucines 1 and 2) have been achieved from d-3-hydroxyleucine and allo-d-3-hydroxyleucine, respectively, through the formation of the corresponding N-Cbz β-lactones, followed by a ring opening promoted by lithium chloride and a debenzylation process.     

The first stereoselective total synthesis of (3S,4R)-dihydroxy-(6S)-undecyl-α-pyranone and total synthesis of (2S,3R,5S)-(−)-2,3-dihydroxytetradecan-5-olide

The first total synthesis of (3S,4R)-dihydroxy-(6S)-undecyl-α-pyranone 1 and total synthesis of (2S,3R,5S)-(−)-2,3-dihydroxytetradecan-5-olide 2 have been achieved in five steps in a highly stereoselective manner using Maruoka allylation, olefin cross-metathesis, and Sharpless asymmetric dihydroxylation as key steps.     

SmI2-induced cyclization of optically active (E)- and (Z)-β-alkoxyvinyl sulfoxides with aldehydes

SmI₂-induced reaction of (E)-β-alkoxyvinyl (R)- and (S)-sulfoxides with aldehydes effected a highly stereoselective intramolecular cyclization to give 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-tetrahydropyran-3-ols, respectively. The reaction of (Z)-(R)-isomer gave 2,6-syn-2,3-cis-tetrahydropyran-3-ol and a ring-opened product, and that of (Z)-(S)-isomer yielded many products.     

Reagent-controlled diastereoselective synthesis of (2S,3R)- and (2R,3R)-2,3-diaminobutanoic acid derivatives using proline-catalyzed α-hydrazination reaction

(2S,3R)- and (2R,3R)-2,3-Diaminobutanoic acid (Dab) derivatives were efficiently synthesized from Cbz-(R)-alanine using the proline-catalyzed diastereoselective α-hydrazination reaction and the SmI₂-promoted reductive cleavage of the N-N bond as the key steps.     

Concise access to enantiopure (S)- and (R)-α-trifluoromethyl pyroglutamic acids from ethyl trifluoropyruvate-based chiral CF3-oxazolidines (Fox)

A straightforward synthesis of enantiopure (S)- and (R)-α-Tfm-pyroglutamic acid is reported. The strategy is based on the use of a chiral CF₃-hydroxymorpholinone intermediate conveniently obtained from ethyl trifluoropyruvate-based chiral CF₃-oxazolidines (Fox). The key step is an oxidative cyclization followed by a reductive cleavage of the (R)-phenylglycinol chiral auxiliary.     

Synthesis of (3R,4S,5S,9S)-3,5,9-trihydroxy-4-methylundecanoic acid δ-lactone

Radical-mediated opening of a chiral trisubstituted epoxy alcohol using cp₂TiCl furnished the ‘2-methyl-1,3-diol’ moiety with the desired stereochemistry, which led to a total synthesis of (3R,4S,5S,9S)-3,5,9-trihydroxy-4-methylundecanoic acid δ-lactone 1.     

Host compounds (+)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-(−)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation

In this work, we have compared the host abilities of closely related compounds (+)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-(?)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) when these were recrystallized from single and mixed toluidine guests. Significant differences in host behaviour and selectivities were revealed and these were explained by means of single crystal diffraction experiments. Thermal analyses were used to determine the relative complex stabilities, and these data correlated exactly with the host selectivity orders for both TETROL and DMT.     

An efficient deprotection method for 5′-[O,O-bis(pivaloyloxymethyl)]-(E)-vinylphosphonate containing oligonucleotides

5′-(E)-Vinylphosphonate (VP) is an effective bioisostere of the natural 5′-monophosphate in small interfering RNAs (siRNAs). Solid-phase synthesis of VP-siRNAs requires the use of appropriately protected VP-phosphoramidites in combination with optimal oligonucleotide deprotection conditions. Addition of 3% (v) neat diethylamine to the standard aqueous ammonia deprotection conditions allows clean and rapid one-step deprotection of 5′-[O,O-bis(pivaloyloxymethyl)] (POM)-protected VP oligonucleotides, minimizing side reactions and impurities, which broadly enhances the scope of VP oligonucleotide synthesis.     

(S)-Threonine/α,α-(S)-diphenylvalinol-derived chiral ionic liquid: an immobilized organocatalyst for asymmetric syn-aldol reactions

Chiral ionic liquids containing (S)- or (R)-threonine amide and α,α-(S)-diphenylvalinol units were synthesized In the presence of the (S)-threonine-derived catalyst reactions between ketones with secondary carbon atom(s) at the α-position with respect to the carbonyl group and aromatic (heteroaromatic) aldehydes afforded the corresponding syn-aldols in high yields (up to 99%) and with high diastereo-(syn/anti up to 97:3) and enantioselectivity (up to 99% ee), which was maintained over three reaction cycles.     

Orthoamides by selective borohydride reduction of N,N′,N″-triacyl- and N,N′,N″-tri(alkoxycarbonyl)-guanidines

N,N′,N″-Triacylguanidines and N,N′,N″-tri(alkoxycarbonyl)guanidines were prepared and reduced with borohydride salts in a mixture of tetrahydrofuran and acetic acid to give triacyl and tri(alkoxycarbonyl) orthoamides in yields of 40–85%. However, similar reduction of N,N′,N″-tri(t-butoxycarbonyl)guanidine did not give orthoamide but the aminal di(t-butyl) methylenedicarbamate.     

A practical synthesis of the PPARα agonist, (R)-K-13675, starting from (S)-2-hydroxybutyrolactone

A practical synthesis of optically pure PPARα agonist, (R)-K-13675, is described. This process is based on the use of (S)-2-hydroxybutyrolactone, which can be transformed into the requisite n-butyl (S)-2-hydroxybutanoate in an efficient manner. A key reaction is the etherification between the phenol and n-butyl (S)-2-trifluoromethanesulfonyloxybutanoate to give the phenyl ether in excellent yield without loss of optical purity.     

Stereoselective synthesis of (22Z)-25-hydroxyvitamin D2 and (22Z)-1α,25-dihydroxyvitamin D2

Two new vitamin D₂ analogues, (22Z)-25-(OH)-D₂ and (22Z)-1α,25-(OH)₂-D₂, were serendipitously synthesized from vitamin D₂ and using the Julia-Kocienski olefination.     

A novel stereoselective synthesis of (−)-β-conhydrine from (R)-2,3-O-cyclohexylidine glyceraldehyde

A novel stereoselective synthesis of (−)-β-conhydrine is achieved. Stereoselective Grignard reaction of (R)-2,3-O-cyclohexylidine glyceraldehyde with ethyl magnesium bromide, chelation controlled stereoselective Grignard reaction of allyl imine derivative with allyl magnesium bromide, and ring-closing metathesis (RCM) of the diallyl product provides (−)-β-conhydrine in high yield.     

Concise synthesis of enantiopure (S)- and (R)-α-trifluoromethyl aspartic acid and α-trifluoromethyl serine from chiral trifluoromethyl oxazolidines (Fox) via a Strecker-type reaction

A concise synthesis of enantiopure (S)- and (R)-α-Tfm-aspartic acid and α-Tfm-serine is reported. The key step involves a Strecker-type reaction on chiral CF₃-oxazolidines (Fox) derived from ethyl 4,4,4-trifluoroacetoacetate (ETFAA) or ethyl trifluoropyruvate.     

Conformationally restricted analogues of both (S)-β-homoserine and (S)-aspartic acid from chiral 3-acylamino pyrrolidin-2-ones

Starting from chiral 3,4-trans-disubstituted pyrrolidin-2-ones 11a and 11b, obtained from a Baylis-Hillman adduct, conformationally restricted analogues of both (S)-β-homoserine, 17, and (S)-aspartic acid, 21, were synthesized, respectively, and these compounds are suitable either for introduction in peptidomimetics or for synthesis of novel β-foldamers.     

Aerobic copper-catalyzed synthesis of (E)-alkenyl sulfones and (E)-β-halo-alkenyl sulfones via addition of sodium sulfinates to alkynes

Copper-catalyzed sulfonylation of alkynes using sodium sulfinates in air produced regio- and stereoselectively (E)-alkenyl sulfones. When a CuCl catalyst was employed, the hydrosulfonylation proceeded syn-selectively, and (E)-alkenyl sulfones were synthesized in excellent yields. In contrast, the reaction using CuI catalyst produced (E)-β-haloalkenyl sulfones anti-selectively in the presence of potassium halides. Furthermore, the (E)-β-bromoalkenyl sulfones are possible to convert into various alkenyl sulfones by Suzuki–Miyaura coupling.     

Facile synthesis of (Z)- and (E)-3-allylidene-β-lactams via thermal β-elimination of trans-3-allyl-3-sulfinyl-β-lactams

A competent synthetic route for the synthesis of novel (Z)- and (E)-3-allylidene-β-lactams is described. The strategy involves oxidation of trans-3-allyl-3-phenylthio-β-lactams 1 using sodium metaperiodate (NaIO₄) to diastereomeric trans-3-allyl-3-phenylsulfinyl-β-lactams 2 and 3, which further undergo thermal β-elimination in refluxing carbon tetrachloride to furnish (Z)- and (E)-3-allylidene-β-lactams 5 and 6 in good to excellent yields. The molecular structure of 3b has been established with the help of single crystal X-ray analysis.