Julia Coupling Research Articles

Synthesis of 19-norcalcitriol analogs with alkylidene moieties at C-2 based on succinic acid and l-methionine

On the basis of the literature data, our previous research work and docking experiments, we designed novel 19-norvitamin D compounds having elongated 2-alkylidene substituents. These 19-norcalcitriol derivatives have attached 2-(3′-aminopropylidene) substituent in which the nitrogen atom bears acyl residue derived from succinic acid and l-methionine. Both compounds were obtained by the same synthetic strategy involving Julia coupling of the A-ring ketone with the known C/D-ring sulfone. In the obtained 1α,25-dihydroxy-19-norvitamin D3 derivative, the alkylidene substituent at C-2 was further elaborated to the desired structures.

Total Synthesis of (+)-Panacene.

The first total synthesis of the naturally occurring enantiomer of the marine bromoallene (+)-panacene is described. Central to this concise enantioselective synthesis was the use of a Noyori transfer hydrogenation for a Dynamic Kinetic Resolution (DKR) that set the desired absolute stereochemistry. A highly stereoselective Julia coupling was then used to install a Z-configured enyne, which enabled the biomimetic construction of the axially chiral bromoallene.

ChemInform Abstract: Total Syntheses of Heliannuols: An Overview

AbstractReview: [41 refs.

Synthesis and biological activity of two C-7 methyl analogues of vitamin D.

Two novel vitamin D analogues of the hormone 1α,25-(OH)2D3 modified at C-7, namely, 7-methyl-1α,25-(OH)2D3 (12) and 7-methyl-1α,25-(OH)2-19-nor-D3 (26), were synthesized and biologically evaluated to gain further insights into the structure-function relationships of vitamin D. Key steps in the synthesis of 12 include the functionalization at C-7 by an efficient regioselective hydrostannylation of an allene precursor, and the construction of the triene framework by a palladium-catalyzed intramolecular cyclization-Suzuki-Miyaura coupling cascade. Since the calcitriol analogue 12 was prone to conversion into its previtamin D form by thermal equilibration, the corresponding 19-nor-compound 26 was also synthesized. The diene moiety of compound 26 was constructed by a modified Julia coupling. UV data as well as X-ray analysis indicate that introduction of the methyl group at C-7 results in a significant deviation from planarity of the 5,7-diene moiety. The new vitamin D analogues 12 and 26 retained good VDR binding ability.

Synthesis of the Polyketide (E)-Olefin of the Jamaicamides

The jamaicamides, isolated in Jamaica from the cyanobacterium Lyngbya majuscula, are new mixed polyketide-peptides that are known to be sodium channel blockers. The polyketide moiety contains an (E)-vinyl chloride, an undetermined methyl stereocenter (C9), and an (E)-olefin. Herein, we report the synthesis of the (E)-olefin moiety of the polyketide of the jamaicamides utilizing a Kocienski–Julia coupling. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

Total Synthesis of the Nominal Didemnaketal A

False identity: The synthesis of a natural product described by Faulkner and co-workers two decades ago has revealed the need for the revision of some stereochemical assignments. The key steps in this flexible route, which could provide access to stereodefined analogues for biological evaluation, included a Julia coupling, a Suzuki-Miyaura reaction, and Wittig olefination (see scheme; MOM, PMB, and TBS are protecting groups). Copyright

ChemInform Abstract: Synthesis of Chalcones and Flavanones Using Julia—Kocienski Olefination.

AbstractArylethanones of type (I) and (IV) are applied as Julia coupling partners for the reaction with aromatic aldehydes to give chalcones and flavanones, correspondingly.

ChemInform Abstract: Synthesis of a Model Compound of Corydendramine A via a Julia Coupling.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

New 1α,25-dihydroxy-19-norvitamin D 3 analogs with a frozen A-ring conformation

We have recently described the synthesis of 1α,25-dihydroxy-19-norvitamin D 3 analogs 2 and 3, possessing an additional ring connecting their 3β-oxygen and C-2. Such structural constrains prevent the A-ring conformational flexibility and the analogs exist exclusively in the α-chair form with their 1α-hydroxy groups fixed in the axial position. The analogs bind very poorly to vitamin D receptor and are devoid of transcriptional activity. Rather unexpectedly, when tested in vivo in rats, they exhibited calcemic response significantly delayed compared to 1α,25-dihydroxyvitamin D 3 ( 1). Such a response might be due to the metabolic conversion (ether cleavage?) of these compounds in the living organisms. It was therefore of interest to obtain and evaluate biologically the analogous compounds having an additional ring of purely hydrocarbon nature. Such analog 4 of 1α,25-dihydroxy-19-norvitamin D 3, characterized by the presence of an equatorial 1α-hydroxy group (β-chair form), has been synthesized by us and tested biologically. The geometrical isomer 5 having a fixed 3β-hydroxy group was also obtained. These compounds were formed in the Julia coupling of the sulfone derived from the Grundmann ketone, and the A-ring fragment prepared in the multi-step synthesis from the (−)-quinic acid. Contrary to its counterpart 5, the analog 4 retained some affinity to vitamin D receptor.

Studies on the Synthesis and Metabolism of 14-epi-2α-(3-Hydroxypropyl)-19-norvitamin D3 and Its 2β-Isomer

Two derivatives of 14-epi-1α,25-Dihydroxy-19-norvitamin D 3 , epi-2α-(3-hydroxypropyl)-1 α,25-dihydroxy-19-norvitamin D 3 14-epi-MART-10) and its 2-epimeric analog (14-epi-MART-11), were synthesized using Julia coupling reaction to connect between the C5 position (steroidal numbering) of an A-ring precursor ketone derived from (-)-quinic acid i the C6 position of a protected 14-epi-CD-ring benzothiazole sulfone. The coupling and deprotection reactions generated a mixture of 14-epi-MART-10 and 14-epi-MART-11 in a moderate yield. The C2-isomers were then separated as ir pivalate forms. The C2-stereochemistry of 2α- and 2β-isomers was.

Total Synthesis of Amphidinolide Q

Asymmetric synthesis of amphidinolide Q, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp., has been accomplished with Julia coupling, Myers alkylation, and Yamaguchi lactonization. The absolute configuration of amphidinolide Q was confirmed to be 1 from comparison of the NMR data and [alpha](D) values of synthetic and natural amphidinolide Q.

Synthesis of a Model Compound of Corydendramine A via a Julia Coupling

The synthesis of the tetraenylpiperidine 12, which has the same core structure as the natural product corydendramine A, has been completed in eight steps starting from 2-piperidinemethanol 3 and trans,trans-2,6-nonadienal 6. The key step of the synthesis was a Julia coupling of sulfone (10) with aldehyde (5) to form a conjugated triene.

New 1α,25-Dihydroxy-19-norvitamin D3 Compounds Constrained in a Single A-Ring Conformation: Synthesis of the Analogues by Ring-Closing Metathesis Route and Their Biological Evaluation

Vitamin D compounds possessing A rings prohibited from flipping to the alternative chair form (i.e., analogues 2 and 26) were synthesized. The bicyclic fragment 22 consisting of the fused cyclohexane and dihydropyran rings was constructed via the ring-closing metathesis route. Also, a homologous synthon 23 with an attached dihydropyran ring was successfully synthesized using this strategy. The carbonyl deprotection in 22 yielded cyclohexanone 5 that was subjected to Julia coupling with the anion of the phenylthiazoline sulfone 25. In the resulting isomeric 19-norvitamins 2 and 26, their A rings can exist only in the alpha- and beta-conformation. The analogue 26 was 300 times more active in binding to the vitamin D receptor protein, 30 times more effective in causing HL-60 differentiation, and 10 times more active in transcription. These results confirm that the beta-chair form of the vitamin D ring A is necessary for the binding to the receptor.

Synthesis and structure revision of tyroscherin, and bioactivities of its stereoisomers against IGF-1-dependent tumor cells

Synthesis of the proposed structure of tyroscherin, a growth inhibitor of IGF-1-dependent cancer cells, was succeeded by one-pot Julia coupling. However, spectral data of the synthetic compound were not identical with those of natural tyroscherin. The stereochemistry of tyroscherin is revised to be 2 S,3 R,8 R,10 R by syntheses of stereoisomers. Synthetic tyroscherin showed more potent activity than its stereoisomers against IGF-1-dependent cancer cells.

Synthesis and structure revision of tyroscherin, a growth inhibitor of IGF-1-dependent tumor cells

Synthesis of the proposed structure of tyroscherin, a growth inhibitor of IGF-1-dependent cancer cells, was succeeded by one-pot Julia coupling. However, spectral data of the synthetic compound were not identical with those of natural tyroscherin. The stereochemistry of tyroscherin was revised to be 2 S,3 R,8 R,10 R by syntheses of stereoisomers.

Total Synthesis of Leustroducsin B

Leustroducsin B was synthesized via a convergent route based on division of the leustroducsin molecule into three segments A, B, and C. Two coupling reactions (Julia coupling reaction and Nozaki-Hiyama-Kishi (NHK) reaction) were employed for coupling of segments A and B: segment A1 for the Julia coupling reaction was prepared by a combination of Sharpless asymmetric epoxidation and an epoxide-cleavage reaction with an organoaluminum reagent, while segment A2 for the NHK reaction was synthesized from optically active alcohol that had previously been prepared by lipase-catalyzed kinetic resolution. Segment B, whose structure was modified with some functional groups, was synthesized from (R)-malic acid by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation, and segment C, containing a cyclohexane moiety, was prepared by asymmetric Diels-Alder reaction. Segment B was first coupled with segment A1 via the Julia coupling reaction, but the yield was low due to unexpected epimerization. The NHK reaction of segment A2 proceeded to give the coupling product in good yield. This product was coupled with segment C via Wittig and Stille coupling reactions, and finally, phosphorylation was carried out by partial hydrolysis of a cyclic phosphate to give leustroducsin B.

Design, Synthesis, and Biological Evaluation of a 1α,25-Dihydroxy-19-norvitamin D3 Analogue with a Frozen A-Ring Conformation

To establish the conformation of vitamin D compounds responsible for biological activity, a 1alpha,25-dihydroxy-19-norvitamin D analogue 4 possessing a 1alpha-hydroxy group fixed in the axial orientation (beta-chair form) was synthesized. The starting compounds were bicyclic lactones 6, 7a, and 7b, derived from the quinic acid lactone, which were converted to the bicyclic ketone 13. Julia coupling of this compound with sulfone 15 produced the 19-norvitamin D analogue 4, possessing an additional ring connecting the 3beta-oxygen and C-2, and the isomeric 3beta-hydroxy compound 5. In vitro, both analogues 4 and 5 exhibit reduced activity compared to the natural hormone 1, but the binding, differentiation, and transcriptional activities of analogue 5 are markedly higher than that of 4 constrained in the alpha-chair conformation. Surprisingly, in vivo tests in mice showed that the analogue 4 significantly increases serum calcium at dose levels similar to 1alpha,25-(OH)2D3. These seemingly discordant results are discussed.

New Total Synthesis of (+)‐Ambrein.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Total synthesis of leustroducsin B via a convergent route

Total synthesis of leustroducsin B was achieved via a convergent route, which includes Julia coupling reaction of segment A with segment B followed by Stille coupling reaction of segment C.

Alternative Synthesis of Cystothiazole A.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.