d-2-Deoxy-2-fluoro-chiro-inositol—a new member of the deoxy fluoro inositol family

An efficient synthetic route to d-2-deoxy-2-fluoro-chiro-inositol has been developed with inversions of the C-1 and C-5 configuration of l-quebrachitol. The key steps of the route are two consecutive one pot epimerization procedures which do not require time-consuming protecting groups chemistry.     

Stereoselective synthesis of the C31-C39 unit of (+)-phorboxazoles from m-anisaldehyde

A stereoselective route for the synthesis of the C31-C39 fragment of (+)-phorboxazoles is described. The route features Birch reduction, ozonolysis and acid-catalysed cyclisation of enantiopure precursors as key transformations to give the tetrahydropyran ring, starting from m-anisaldehyde as a masked β-keto ester to obtain the pyran skeleton of compound 1.     

A proline-catalyzed aldol approach to the synthesis of 1-N-iminosugars of the d-glucuronic acid type

A new synthetic route to 1-N-iminosugars of glucuronic acid type (e.g., 1) has been developed employing proline-catalyzed aldol reaction as a key step.     

Synthesis of the quorum sensing molecule Diffusible Signal Factor using the alkyne zipper reaction

The development of a concise synthesis of the quorum sensing molecule Diffusible Signal Factor is described. This route exploits an alkyne zipper reaction to form a key terminal alkyne intermediate. The chemistry outlined here may also be applied to the preparation of cis-unsaturated analogues of Diffusible Signal Factor.     

The second-generation synthesis of BICMAP analogues

We previously reported the synthesis of BICMAP (1a) via 6-diphenylphosphino-2,3-dihydrobenzofuran as a key intermediate. However, we did not successfully synthesize BICMAP analogues via a similar synthetic route. Herein we report the second-generation synthesis of BICMAP and its derivatives via diethylphosphonate as a key intermediate.     

A flexible synthesis of C-6 and N-1 analogues of a 4-amino-1,3-dihydroimidazo[4,5-c]pyridin-2-one core

A flexible route which enables access to derivatives of 4-amino-1,3-dihydroimidazo[4,5-c]pyridin-2-ones is described. Issues of selectivity, reaction safety, and low yields in original routes are overcome with the key improvements to the route, including a Negishi cross-coupling and use of a carbamate as a protecting group and intrinsic carbonyl source. The new route enables variation of C-6 and N-1 substituents.     

Synthetic studies directed toward guianolides: an organoiron route to the 5,7,5 tricyclic ring system

A diastereoselective route to the 5,7,5-tricyclic core of the guianolides is presented. This route relies on Cope rearrangement of a divinylcyclopropane prepared by alkenyl Grignard addition to a (pentadienyl)iron(+1) cation, followed by oxidative decomplexation. An additional key reaction involves oxidative rearrangement of a 3,4-epoxy-1,7-diol to generate a γ-lactone. The relative stereochemistry of this product was established by X-ray crystallography.     

Stereocontrolled metalloenamine alkylations: application to the asymmetric synthesis of 4-alkyl-1,2,3,4-tetrahydroisoquinolines

A procedure for the asymmetric synthesis of 4-alkyl-1,2,3,4-tetrahydroisoquinolines is described. The key step in the synthetic route is a stereocontrolled metalloenamine alkylation using (R)-(+)-phenylglycinol methyl ether as the chiral auxiliary. Subsequent N-methylation, hydrogenolysis and cyclization afforded the target heterocycles with enantiomeric excesses higher than 99%.     

A stereodivergent route to epimeric 2-piperidinylglycines: application to the synthesis of carbocyclic β-lactam derivatives

A route to two epimeric hitherto unknown 2-piperidinylglycine derivatives, as precursors of carbocyclic β-lactam derivatives, has been developed, which features diastereoselective addition of allyl metal reagents to an N-allylimine derivative of Garner’s aldehyde and ring-closing metathesis as key steps.     

Studies into the generation and Diels-Alder reactions of 7,8-quinolyne with furan dienes

Reaction of an appropriate ortho-halo tosylate precursor with organolithium reagents provides the first conclusive route to the intermediate, 7,8-quinolyne. The transient existence of this hetaryne was confirmed by Diels-Alder reactions with furan derivatives that provide endoxide adducts. Chemical induced rearrangement of these adducts allows entry to key compounds of 10-hydroxy[h]benzoquinoline and its 7-substituted derivatives in modest yields.     

Convenient synthesis of epimeric indolizidines by the intramolecular 1,3-dipolar cycloaddition of a sugar derived N-(3-alkenyl)nitrone

The stereoselective synthesis of two epimeric penta-hydroxylated indolizidines was accomplished from 2,3:5,6-di-O-isopropylidene-α-d-mannofuranose and N-(2-methylpent-4-en-2-yl)hydroxylamine. The transformation of these substrates into the corresponding 7-oxa-1-azabicyclo[2.2.1]heptane by the intramolecular 1,3-dipolar cycloaddition was the key step of the synthesis. The adduct was transformed into the tricyclic ammonium salt by intramolecular N-alkylation. The tricyclic ammonium salt was converted to the target compounds by: (route 1) the catalytic hydrogenation; or (route 2) the reaction with sodium azide, followed by the enantioselective reduction of the resulting indolizidinone.     

Stereodivergent synthesis of cyclic γ-aminobutyric acid – GABA analogues

A novel synthetic route towards two series of enantiomerically pure cyclic analogues of 2,3-cis- and 2,3-trans-γ-aminobutyric acid (GABA) was developed. The route is based on the elongation and stereodivergent manipulation of a readily accessible enantiomerically pure γ-substituted α-aminolactone. The five-step route towards the 2,3-cis-substituted GABA analogues was achieved via straightforward carbon chain extension of the lactone using a non-classical Wittig reaction followed by chemoselective reduction and a protecting group switch. The five-step route towards the 2,3-trans-substituted GABA analogues employed elongation of the same aminolactone using a Horner-Wadsworth-Emmons reaction and highly stereoselective intramolecular oxa-Michael addition as the key synthetic manipulations. Altogether this chemistry has allowed the stereodivergent preparation of a novel class of GABA analogues in two diastereomeric series.     

Synthetic approach to cis and trans-decalins via Diels—Alder reaction and ring-closing metathesis as key steps: further extension to dioxapropellane derivative by ring-closing metathesis

9,10-Substituted cis and trans-decalins were synthesized by a simple route using the Diels-Alder reaction and ring-closing metathesis (RCM) as key steps. Later, the cis-decalin system has been extended to 3,8-dioxa[8.4.4]propellane derivative by RCM sequence as a key step.     

A novel synthesis of N-(piperidin-4-yl)-1,3-dihydroindol-2-one via an intramolecular Pd-catalyzed amination

A novel efficient synthetic route to the pharmaceutical key intermediate N-(piperidin-4-yl)-1,3-dihydroindol-2-one is described. The key step involves a high-yielding intramolecular palladium-catalyzed amination reaction using Buchwald’s X-Phos ligand under mild reaction conditions.     

Studies on the Enantioselective Synthesis of E-Ethylidene-bearing Spiro[indolizidine-1,3′-oxindole] Alkaloids

A synthetic route for the enantioselective construction of the tetracyclic spiro[indolizidine-1,3′-oxindole] framework present in a large number of oxindole alkaloids, with a cis H-3/H-15 stereochemistry, a functionalized two-carbon substituent at C-15, and an E-ethylidene substituent at C-20, is reported. The key steps of the synthesis are the generation of the tetracyclic spirooxindole ring system by stereoselective spirocyclization from a tryptophanol-derived oxazolopiperidone lactam, the removal of the hydroxymethyl group, and the stereoselective introduction of the E-ethylidene substituent by acetylation at the α-position of the lactam carbonyl, followed by hydride reduction and elimination. Following this route, the 21-oxo derivative of the enantiomer of the alkaloid 7(S)-geissoschizol oxindole has been prepared.     

A furan route to the asymmetric synthesis of trans-fused polyether building blocks

A novel route towards chiral trans-fused polyether lactones 7 and 12 has been developed starting with commercially available furfural. Sharpless kinetic resolution and ring-closing metathesis reactions served as key steps in the strategy.     

The biosynthesis of the fungal meroterpenoids boviquinone-3 and -4 follows two different pathways

A key step in the biosynthesis of the fungal meroterpenoids boviquinone-3 and -4 is the prenylation of 3,4-dihydroxybenzoic acid. In fruit-bodies of Suillus bovinus boviquinone-4 is formed by geranylgeranylation of 3,4-dihydroxybenzoic acid at C-5, whereas in Chroogomphus rutilus the farnesyl side chain of boviquinone-3 is introduced at C-2. The biosynthesis of the terpenoid chain of boviquinone-4 follows the mevalonate route.     

Total synthesis of the fully lipidated glycosylphosphatidylinositol (GPI) anchor of malarial parasite Plasmodium falciparum

We report a new and convergent strategy for the total synthesis of fully lipidated glycosylphosphatidylinositol (GPI) anchor, the major pro-inflammatory factor of malarial parasite (Plasmodium falciparum). The key features of our approach include, the access to the key glucosamine-inositol intermediate by a novel route without a priori resolution of myo-inositol, convergent assembly of the tetramannose glycan domain, flexibility for the placement of the three fatty acids in the desired order in the final steps, and the opportunity to construct GPI analogues/mimics to probe the biosynthesis, immunology and cell biology of the GPI anchor pathway in the malaria parasite.     

Synthesis of novel thiol taxoids based on the 7,10-di-(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III: both the syn and anti 10-deacetyl-2′-deoxy-2′-mercaptopaclitaxels

Two new kinds of docetaxel compound, with a mercapto group instead of the hydroxyl on the C13 side chain (both syn and anti), via the 7,10-di-(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III route, were synthesized. The uses of trans and cis oxazoline compounds, and their stereoselective ring-opening reactions with thiolacetic acid, were proved to be key steps.     

Regiocontrolled synthesis of highly-functionalized fused imidazoles: a novel synthesis of second generation LFA-1 inhibitors

A new and reliable route to a new class of LFA-1 inhibitors such as (2) has been developed. A key aspect of this route is the transformation of amino amide 5 into iodide 3 in four steps. Iodide 3 is a key advanced intermediate used in the synthesis of all second-generation 1H-imidazo[1,2-α]imidazol-2-one LFA-1 inhibitors.