Asymmetric syntheses of (1R,1R,5R,7R) and (1S,1R,5R,7R)-1-hydroxy-exo-brevicomin and a formal synthesis of (+)-exo-brevicomin

Asymmetric syntheses of (1R,1^′R,5^′R,7^′R) and (1S,1^′R,5^′R,7^′R)-1-hydroxy-exo-brevicomins 1 and 2, volatiles of the male mountain pine beetle, and a formal synthesis of (+)-exo-brevicomin 3, a component of the attracting pheromone system of several bark beetles have been achieved. The key steps are Birch reduction of commercially available α-picoline, selective Wittig olefination, and Sharpless asymmetric dihydroxylation.     

Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin

A convergent synthesis of (4R,15R,16R,21S)-rollicosin (1) and (4R,15S,16S,21S)-rollicosin (2) was accomplished. Hydroxy lactone 6a and/or 6b were synthesized from 4-pentyn-1-ol, and α,β-unsaturated lactone 7 was synthesized from γ-lactone 8 and 5-hexen-1-ol. Inhibitory activity of these compounds was examined with bovine heart mitochondrial complex I.     

Stereoselective synthesis of (+)-(1R,2S,5S,7R)-2-hydroxy-exo-brevicomin

A stereoselective approach for the synthesis of (+)-(1R,2S,5S,7R)-2-hydroxy-exo-brevicomin from l-ascorbic acid has been described. The key steps are highly stereoselective nucleophilic addition reaction on aldehyde 8 and also a single pot transformation of 15 to (+)-(1R,2S,5S,7R)-2-hydroxy-exo-brevicomin. The later tandem reaction which involves the hydrogenation of double bond, debenzylation, MOM deprotection and bicyclic ketal formation was carried under Pd/C, H₂ followed by acid treatment.     

Concise and practical synthesis of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6-iminosugars

The syntheses of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6 iminosugars 1a and 1b, respectively, from d-glucose are described. The key transformations in this reaction sequence include regio-selective epoxide ring opening with N-benzylamine followed by intramolecular reductive amination of amino-aldehyde.     

A stereoselective approach for the total synthesis of (5R,7R,9R)-7,9-dihydroxy-5-decanolide#

A stereoselective approach for the total synthesis of lactone (5R,7R,9R)-7,9-dihydroxy-5-decanolide is described. The sequence of synthetic reactions involves a Keck asymmetric allylation, diastereoselective iodo-carbonate cyclization, regioselective ring-opening reaction, oxidative lactonization.     

Stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucines

A stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucine is disclosed. The key step of the reaction sequence involves, stereo- and regioselective bromohydration of 7, using a brominating agent derived in situ from N-bromosuccinimide and 2,6-lutidine, via intramolecular sulfinyl group participation.     

Synthetic studies on homophymine A: stereoselective synthesis of (2R,3R,4R,6R)-3-hydroxy-2,4,6-trimethyloctanoic acid

An efficient and highly stereocontrolled synthesis of (2R,3R,4R,6R)-3-hydroxy-2,4,6-trimethyloctanoic acid, the β-hydroxy acid unit that acylates the N-terminus of homophymine A, has been devised starting from iodoethane and (S,S)-pseudoephedrine propionamide in 9 steps and 36% average overall yield. Comparison of the ¹H and ¹³C NMR and optical rotation data of the resulting β-hydroxy acid with the natural fragment unambiguously verifies the configurational assignment as (2R,3R,4R,6R).     

(5R,7R)-5-Methylheptadecan-7-ol: a novel sex pheromone component produced by a female lichen moth, Miltochrista calamina, in the family Arctiidae

A methyl-branched heptadecanol was found in the pheromone gland extract of a female lichen moth, Miltochrista calamina (Arctiidae, Lithosiinae). GC-MS analyses of the alcohol and a hydrocarbon derived from it by subsequent treatments with methanesulfonyl chloride and LiAlD₄ in microscale reactions indicated 5-methylheptadecan-7-ol (1) as one possible structure. The four stereoisomers of 1 in a ratio of 4:4:1:1 were prepared from (S)-β-citronellol with 60% ee, and were separated by a combination of achiral and chiral HPLC columns. The absolute configuration of each isomer was determined by the comparison with the chromatographic behaviors of other samples synthesized by a different scheme, which applied the Jacobsen hydrolytic kinetic resolution of racemic 1,2-epoxydodecane to fix the configuration of the 7-hydroxy group. Only the (5R,7R)-isomer attracted male moths; thus, we concluded that M. calamina females secrete (5R,7R)-1 as a sex pheromone, indicating a new chemical class of lepidopteran female sex pheromones.     

A chiron approach to (1R,2R,5S,7R)-2-hydroxy-exo-brevicomin, a component of the volatiles produced by the male mountain pine beetle, Dendroctonus ponderosae

A chiron approach to a synthesis of (1R,2R,5S,7R)-2-hydroxy-exo-brevicomin 1, a component of the volatiles obtained from male mountain pine beetles, Dendroctonus ponderosae has been achieved. Our synthesis started with commercially available d-mannitol and involved Wittig olefination, acid catalysed one-pot hydrogenation and internal acetalization as key steps.     

Practical, efficient, stereoselective, formal synthesis of (2R,3R,4R)-3-hydroxy-4-methylproline

A highly efficient and stereoselective synthesis of (2R,3R,4R)-HMP is disclosed employing the sulfinyl group as an internal nucleophile to functionalize an olefin in the key step of the reaction sequence. The proline ring is elaborated by a (4C+N) cyclization.     

Easy route to labeled and unlabeled R,R,R-γ-tocopherol by aryl demethylation of α-homologues

The interest in vitamin E research is increasingly focusing on the peculiar properties of the less investigated tocopherols and their metabolites, such as γ-tocopherol, which have been revealed as very important for human health. Metabolic studies of γ-tocopherol have been constricted by its high cost and the poor availability of stable isotope-labeled forms. An efficient, inexpensive and simple route is described for the preparation of labeled and unlabeled R,R,R-γ-tocopherol, starting from R,R,R-α-tocopherol, through simple thermal decarboxylation of γ-tocopherol-5-carboxylic acid.     

(2S,5R/2R,5S)-Aminoethylpipecolyl aepip-aegPNA chimera: synthesis and duplex/triplex stability

This article reports the design and facile synthesis of novel chiral six-membered PNA analogues (2S,5R/2R,5S)-1-(N-Boc-aminoethyl)-5-(thymin-1-yl)pipecolic acid, aepipPNA IV that upon incorporation into standard aegPNA sequences effected stabilization of complexes with complementary target DNA. Substitution of aegPNA unit by the designed monomer at the C-terminus was more effective than substitution at N-terminus. The stabilizing behaviour improved with degree of substitution and was found to be dependent on their relative positions in the sequence. The six-membered piperidine ring in the design may freeze the rigid chair conformations and the relative stereochemistry of the substituents may in effect direct the complex formation with DNA/RNA by sequence-specific nucleobase recognition. In the present aepipPNA analogues, the l-trans stereochemical disposition of the substituents seems to lead to the favorable pre-organization of the PNA oligomers for complex formation with DNA. The results reported here further expand the repertoire of cyclic PNA analogues.     

Synthesis of (4R,8R)- and (4S,8R)-4,8-dimethyldecanal: the common aggregation pheromone of flour beetles

The synthesis of (4R,8R)- and (4S,8R)-4,8-dimethyldecanal 1 and 1a has been achieved connecting the chiral building block (R)-2-methyl-1-bromobutane 4 with (R)- and (S)-citronellol derivatives. The key intermediate 4 was obtained optically pure in five steps from methyl (S)-3-hydroxy-2-methylpropionate 2.     

A flexible route to immunosuppressive agent FR252921. Asymmetric total synthesis of its (13R,14R,19R)-isomer

A flexible route to the proposed structure of FR252921, a novel immunosuppressive agent, is developed. The key elements include the assembly of its two β-hydroxy acid residues via asymmetric aldol condensation of N-acylthiazolidinethinones with aldehydes, and its triene part via a CuI/N,N-dimethylglycine catalyzed Sonogashira coupling and subsequent isomerization. Using this strategy (13R,14R,19R)-FR252921 is elaborated.     

Synthesis of dihydroxylated prolines and iminocyclitols from five-membered endocyclic enecarbamates. Total synthesis of the potent glycosidase inhibitor (2R,3R,4R,5R)-2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP)

cis- and trans-3,4-Dihydroxylated prolines and the iminocyclitol 1,4-dideoxy-1,4-imino ribitol were synthesized employing a strategy involving the Heck arylation of five-membered endocyclic enecarbamates with aryldiazonium salts followed by oxidative cleavage of the electron-rich aromatic ring. The total synthesis of the potent α- and β-glucosidase inhibitor (2R,3R,4R,5R)-2,5-hydroxymethyl-3,4-dihydroxypyrrolidine (DMDP) was also achieved by the same strategy in ten steps from a chiral five-membered enecarbamate in 12% overall yield.     

Asymmetric ring-opening reaction of azabenzonorbornadienes with phenols promoted by palladium/(R,R)-DIOP complex

An efficient asymmetric ring opening reaction of azabenzonorbornadienes with various phenols using Palladium/(R,R)-DIOP complex has been demonstrated, the reaction afforded the corresponding products in excellent yields (80–95%) with moderate enantioselectivities (50–64% ees). The syn-configuration of the product was confirmed by the single X-ray crystallography.     

Stereoselective synthesis of rac-(8R,13S,14S)-7-oxa-estra-4,9-diene-3,17-dione

The first synthesis of a novel oxa-steroid, rac-(8R,13S,14S)-7-oxa-estra-4,9-diene-3,17-dione has been achieved via stereoselective catalytic hydrogenation of the tetra-substituted indene intermediate, whose structure was confirmed by X-ray crystallography. In contrast to the previous reports of similar indene systems, it was found that catalytic hydrogenation of indenes with a large substituent at the C-2 position and a bulky β-oriented protective group at the C-6 position resulted in cis-indanes instead of trans-indanes.     

Synthesis and absolute configuration of two diastereoisomeric (1R,2S,3R)-and (1S,2S,3R)-2-amino-1-(2-furyl)-1,3-butandiols

The synthesis of (1R, 2S, 3R) and (1S, 2S, 3R)-2-(N-benzoylamino)-1-(2-furyl)-1, 3-butandiols (15) and (16) from D-threonine is described. The assignment of absolute configuration of the newly formed asymmetric center at C-1 was based on the ¹H-NMR spectra of O-isopropylidene derivatives 17 and 18.     

An efficient stereoselective synthesis of (2S,4S,5R)-(−)- and (2R,4R,5S)-(+)-bulgecinine

A short synthetic route to (−)-and (+)-bulgecinine, the amino acid moiety of the bulgecins was achieved from the readily available nonchiral pool starting material cis-2-butene-1,4-diol in which a Claisen orthoester rearrangement and a Sharpless asymmetric dihydroxylation were used as the key steps.     

Highly stereoselective allylic ethylation with alkoxytitanacyclopropane reagents. Synthesis of (1R/S,7R)-1,7-dimethylnonyl propanoate, the Western corn rootworm sex attractant

Allylic ethylation of 2-((E)-dodec-2-en-4-yloxy)tetrahydro-2H-pyran with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide proceeds via a S_N2′ pathway to afford (E)-3-methyltridec-4-ene with excellent syn-diastereoselecivity. This transformation is used as a key step in the synthesis of (1R/S,7R)-1,7-dimethylnonyl propanoate, the Western corn rootworm (Diabrotica virgifera virgifera) sex attractant.