A short and concise synthetic route to (−)-coniceine

(−)-Coniceine, the simplest framework of indolizidine alkaloids, has been successfully accessed using a route in which ruthenium-catalyzed ring-closing olefin metathesis (RCM) was the key reaction to establish the unsaturated bicyclic lactam system.     

A convenient new and efficient commercial synthetic route for dasatinib (Sprycel®)

A new and efficient synthetic route for dual-Src/Abl kinase inhibitor dasatinib (Sprycel®), an anticancer drug, is described. This commercially viable process yields dasatinib monohydrate free of potential impurities with consistent yield of 68% in route A and 61% in route B with HPLC purity >99.80% over four stages.     

An efficient synthetic route to functionalized δ-lactams

This paper describes a convenient synthesis of disubstituted functionalized δ-lactams based on Michael addition of primary amines to dimethyl-E-2-alkylidene glutarates 2 followed by an intramolecular cyclisation.     

A furan route to (−)-exo-isobrevicomin

A new enantiocontrolled synthesis of (−)-exo-isobrevicomin, isolated from male mountain pine beetles, Dendroctonus ponderosae, has been established starting from 5-ethyl-2-furfural by employing AD-mix-induced asymmetric induction and oxidative furan ring-expansion reaction as the key steps.     

Semisynthesis of (+)- and (−)-goniomitine from (−)- and (+)-vincadifformine

The first biomimetic semisynthesis of goniomitine has been accomplished in nine steps with 11% overall yield starting from vincadifformine. Natural (?)- and unnatural (+)-goniomitine were prepared from (+)- and (?)-vincadifformine, respectively. The evaluation of the antiproliferative effect of both enantiomers proved unnatural (+)-goniomitine to be more potent, but this enantiomer as well as some close derivatives displayed a moderate activity only.     

An efficient synthesis of enantiopure (+)- and (−)-3-exo-amino-7,7-dimethoxynorbornan-2-exo-ols

We describe the synthesis of new amino alcohols (+)- and (−)-3-exo-amino-7,7-dimethoxynorbonan-2-exo-ols. The (+)- or (−)-7,7-dimethoxy-1,4,5,6-tetrachlorobicyclo[2.2.1]hept-5-en-2-endo-ol, obtained from the enzyme catalysed transesterification of the racemate, was reduced and dechlorinated (Na/NH₃; ethanol), followed by pyridinium chlorochromate oxidation of the resultant alcohols to the corresponding ketones. After treatment with t-BuOK/BuONO, in a nitrosation reaction, α-keto oximes were obtained. Reduction over two steps with NaBH₄ and NaBH₄/NiCl₂·6H₂O followed by in situ acetylation furnished the corresponding acetamido esters, which were hydrolysed with CH₃OH/Na to produce the enantiopure amino alcohols in good yields.     

Asymmetric synthesis of (−)- and (+)-neodichroine/hydrachine A from (+)- and (−)-febrifugine

A new asymmetric approach to both enantiomers of the quinazolinone-containing natural product febrifugine is reported. Utilising a proline-mediated aminooxylation-Horner-Wadsworth-Emmons sequence provides the key optically active 2,3-disubstituted piperidine intermediate 7 in high enantioselectivity but poor overall yield (7 steps, 3%, 98% ee). This intermediate has been used to prepare both naturally occurring (+)-febrifugine (1) and its (?)-enantiomer. In turn, each were then used to synthesise, for the first time, both enantiomers of the claimed natural product neodichroine/hydrachine A. Spectroscopic data for the synthetic compound matched the claimed structure. However, the specific rotation differed in both magnitude and sign from the isolation work.     

Short and efficient synthetic route to methyl α-trioxacarcinoside B and anomerically activated derivatives

A 9-step synthetic route to the complex carbohydrate methyl α-trioxacarcinoside B from 2-acetylfuran is described. Anomerically activated forms, including 1-phenylthio, 1-O-(4'-pentenyl), 1-fluoro, and 1-O-acetyl derivatives are also prepared.     

A synthetic route to 4-alkyl-α-methylhydrocinnamylaldehydes

Research on Chemical Intermediates - The 4-Alkyl-α-methylhydrocinnamylaldehydes (alkyl-isopropyl, isobutyl, methyl) are frequently used fragrances with desired floral (lilac, cyclamen,...     

A novel and efficient synthesis of (+)- and (−)-trans-2-aminocyclohexanol by enzymatic hydrolysis

Both enantiomers of trans-2-aminocyclohexanol were obtained by enzymatic hydrolysis of (±)-2-azidocyclohexanoates using lipases and subsequent hydrogenation.     

A new efficient synthesis of oseltamivir phosphate (Tamiflu) from (−)-shikimic acid

New synthesis of oseltamivir phosphate was accomplished in 9 steps with a 27% overall yield from a readily available (?)-shikimic acid. Selective ring opening reaction of ketal and azide Mitsunobu reaction for facile replacement of a hydroxyl group by the N3 group at the C-3 position of (3R,4R,5R)-ethyl 4-hydroxy-5-(methoxymethoxy)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 4 and at the C-4 position of (3R,4S,5R)-ethyl 4-acetamido-5-hydroxy-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 7 successfully served as the key steps.     

A flexible synthetic route to isoxazolidine β-proline analogs

The function and higher order structure of β-proline oligomers have been relatively unexplored compared to other foldamer classes due in part to synthetic challenges associated with substituted monomers. Here we report a flexible synthesis of di- and trisubstituted isoxazolidine β-proline monomers that enables access to a wide range of densely functionalized analogs suitably protected for solid-phase synthetic protocols. This strategy utilizes chiral isoxazolines as key intermediates and can readily provide single stereoisomers of the target molecules.     

Stereocontrolled synthesis of enantiopure anticancer cyclopentenone prostaglandin analogues: (−)- and (+)-TEI-9826

The synthesis of both enantiomers of TEI-9826 has been accomplished in seven steps with an overall yield of 44% starting from diastereomeric camphor protected 3-[(dimethoxyphosphoryl)methyl]-4,5-dihydroxycyclopent-2-enones. The key steps include a fully diastereoselective hydrogenation of the endocyclic carbon–carbon double bond in the cyclopentenone ring controlled with a chiral diol moiety and the conversion of the latter into a new transposed olefinic bond.     

A new route to α-alkyl-α-fluoromethylenebisphosphonates

A new route to α-alkyl-α-fluoromethylenebisphosphonates, 2 has been developed starting from commercially available tetraethyl fluoromethylenebisphosphonate (1), and alkyl halides using either caesium carbonate in DMF or sodium dimsyl. De-esterification of 2 provided biologically important α-alkyl-α-fluoromethylenebisphosphonic acid, 3, while alkoxide-induced carbon-phosphorus bond cleavage of 2 gave α-fluorophosphonates, 4, which are useful synthons in organic synthesis.     

A simple and efficient stereoselective synthesis of (−)-cleistenolide

A simple and straightforward stereoselective synthesis of α,β-unsaturated δ-lactone, (?)-cleistenolide has been accomplished in 10 steps in an overall yield of 19%, starting from inexpensive and commercially available starting materials, respectively. This linear synthesis utilizes Sharpless asymmetric dihydroxylation, sulfur ylide mediated epoxide opening followed by ring-closing metathesis (RCM) for the formation of six-membered lactone ring as the key step sequence.     

An efficient access to N-tert-butanesulfinyl aldimines in water: Application to one-pot synthesis of homoallylic amines, (+)-crispine A and (−)-coniine

An Efficient method for the syntheses of N-tert-butanesulfinyl aldimines in water was developed using Amberlyst-15 as catalyst. Subsequently, chiral homoallylic amines were synthesized in one pot from aldehydes by combining with In-promoted allylation in aqueous media. The total syntheses of (+)-Crispine A and (?)-Coniine were conducted to demonstrate the utility of this one-pot approach.     

A new synthetic approach based on (−)-menthone for chiral liquid crystals

Starting from (?)-menthone, a new chiral building block useful for liquid crystal preparation was synthesized. This chiral moiety was attached to selected phenols under mild conditions by esterification. Rigid cores of tolanebenzoates and phenylbenzoates were prepared using the palladium cross-coupling reaction or by traditional liquid crystal synthesis methods. This convergent approach ended with a second esterification or palladium cross-coupling reaction to furnish new liquid crystal materials with smectic A, smectic C* and N* phases, as well as blue phases (BP). Thermal behavior, and the effect of chiral moiety branches and molecular packing in the smectic phases, have been investigated using differential scanning calorimetry, optical microscopy and X-ray diffraction.     

A new route to the zizaane sesquiterpenes: An efficient synthesis of (±)-isokhusimone

A novel route to the zizaane sesquiterpene skeleton is demonstrated with a nine-step synthesis of (±)-isokhusimone (2) from norcamphor in an overall yield of 35%. This constitutes a formal synthesis of (±)khusimone (1).     

A new efficient synthesis of pyrazoles from hydrazonoyl halides and β-oxophosphonates

A new practical and efficient synthesis of 1,3,5-trisubstituted pyrazoles has been developed by reacting of hydrazonoyl halides with β-oxophosphonates under mild conditions in good yields with excellent regioselectivity. This process employs an addition–elimination sequence. Wide scope, functional group compatibility has been established.