71065-45-7

Upstream product

• 6213-88-3 3-iodoacrylic acid methyl ester 
• 6214-23-9 methyl (2Z)-3-iodoprop-2-enoate 
• 107-19-7 propargyl alcohol 
• 31930-36-6 ethyl (Z)-3-iodopropenoate 
• 1191-15-7 diisobutylaluminium hydride 
• 31930-36-6 ethyl (E)-3-iodopropenoate 
• 6213-88-3 (E)-methyl 3-iodoacrylate 
• 6372-02-7 (E)-3-iodoacrylic acid 
• 1730-25-2 allylmagnesium bromide 
• 151502-81-7 cis-3-dimethyl(1,1-dimethylethyl)silyloxy-1-iodo-1-propene 
• 1725-82-2 3-iodo-2-propyn-1-ol 
• 82994-41-0 (E)-3-(tri-n-butylstannyl)-2-propen-1-ol 

Downstream Products

• 497-23-4 2-buten-4-olide 
• 313227-83-7 N-[(2Z)-3-iodo-2-propenyl]-p-toluenesulfonamide 
• 87832-31-3 (Z)-1-hydroxypenta-2,4-diene 
• 91060-73-0 (E)-2-decen-4,6-diyn-1-ol 
• 499158-38-2 4-Methoxy-benzoic acid (E)-3-iodo-allyl ester 
• 35042-52-5 (E)-2-penten-4-yn-1-ol 
• 7199-99-7 7-hydroxy-1-phenyl-hept-5E-ene-1,3-diyne 
• 1647100-84-2 (E)-tert-butyl (3-iodoallyl)(tosyl)carbamate 
• 1042150-46-8 (E)-1-(((3-iodoallyl)oxy)methyl)-4-methoxybenzene 
• 97514-97-1 (E)-5-trimethylsilanylpent-2-en-4-yn-1-ol 
• 1197011-09-8 (Z)-1-iodo-3-(4-methoxybenzyloxy)-1-propene 
• 129593-48-2 (Z)-5-phenyl-2-penten-4-yn-1-ol 

Relevant academic research and scientific papers

Inactivation of Medium-Chain Acyl-CoA Dehydrogenase by a Metabolite of Hypoglycin: Characterization of the Major Turnover Product and Evidence Suggesting an Alternative Flavin Modification Pathway

Medium-chain acyl-CoA dehydrogenase (MCAD) is a FAD-dependent enzyme that catalyzes the first step of the fatty acid oxidation cycle.When MCAD is exposed to (methylenecyclopropyl)acetyl-CoA (MCPA-CoA), a metabolite of hypoglycin A and the causative agent of Jamaican vomiting sickness, time-dependent inactivation follows with concomitant bleaching of the active-site FAD.Earlier studies have led to the postulation that the inactivation may involve a spontaneous ring fragmentation induced by a transient α-cyclopropyl radical, and thus suggest a one-electron oxidation pathway.In an effort to find more evidence for the proposed mechanism, we have isolated and characterized the major turnover product, a CoA ester consisting of a disubstituted terminal olefin, an epoxide, and a hydroxymethyl group, from the aerobic incubation mixture of MCPA-CoA and MCAD.Formation of this product may be initiated by trapping the acyclic radical intermediate with O2 to form a transient peroxy radical which, upon receiving one electron from flavin semiquinone followed by an intramolecular epoxidation, gives rise to the observed turnover product.The identification of such a highly oxygenated species as the major turnover product strongly sustains the intermediacy of a ring-opened radical, and as such, the departure from the expected inactivation may directly result from trapping of this radical intermediate by O2.This contention was subsequently substantiated by observing that the partition ratio is nearly 0 under anaerobic incubation.Interestingly, further investigation of the anaerobic inhibition resulted in the discovery of a minor inactivation pathway involving covalent modification of flavin at a locus other than the isoalloxazine ring.Although the chemical nature of the new inhibitor-coenzyme adduct(s) has yet to be elucidated, a structure having MCPA-CoA linked to the N(10) ribityl side chain is appealing.The mechanistic insights derived from this study provide compelling evidence supporting our early notion that inactivation of MCAD by MCPA-CoA is likely to proceed through a radical mechanism.

Synthesis, radiolabeling, and preliminary in vivo evaluation of [68ga] ipcat-nota as an imaging agent for dopamine transporter

Introduction: Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [99mTc]TRODAT-1, [123I]β-CIT, and [123I]FP-CIT are commercially available;99Mo/99mTc generator is in short supply and123I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating68Ga, a radioisotope derived from a68Ge/68Ga generator. Methods: IPCAT-NOTA 22 was synthesized and labeled with [68Ga]GaCl4 ? at room tem-perature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodis-tribution, and dynamic PET imaging studies were performed in Sprague Dawley rats. Results: [68Ga]IPCAT-NOTA 24 obtained had a radiochemical yield of ≥90% and a specific activity of 4.25 MBq/nmol. [68Ga]IPCAT-NOTA 24 of 85% radiochemical purity (RCP%) was stable at 37°C for up to 60 minutes in serum with a lipophilicity of 0.88. The specific binding ratio (SBR%) reached 15.8 ± 6.7 at 60 minutes, and the 85% specific uptake could be blocked through co-injection at 100-and 1000-fold of the cold precursor in in vitro binding studies. Tissue regional distribution studies in rats with [68Ga]IPCAT-NOTA 24 showed striatal uptake (0.02% at 5 minutes and 0.007% at 60 minutes) with SBR% of 6%, 25%, and 62% at 5–15, 30–40, and 60–70 minutes, respectively, in NanoPET studies. The RCP% of [68Ga]IPCAT-NOTA 24 at 30 minutes in vivo remained 67.65%. Conclusion: Data described here provide new information on the design of PET probe of conjugate/pendent approach for DAT imaging. Another chelator or another direct method of intracranial injection must be used to prove the relation between [68Ga]IPCAT-NOTA 24 uptake and transporter localization.

Unified Approach to Furan Natural Products via Phosphine-Palladium Catalysis

Polyalkyl furans are widespread in nature, often performing important biological roles. Despite a plethora of methods for the synthesis of tetrasubstituted furans, the construction of tetraalkyl furans remains non-trivial. The prevalence of alkyl groups in bioactive furan natural products, combined with the desirable bioactivities of tetraalkyl furans, calls for a general synthetic protocol for polyalkyl furans. This paper describes a Michael–Heck approach, using sequential phosphine-palladium catalysis, for the preparation of various polyalkyl furans from readily available precursors. The versatility of this method is illustrated by the total syntheses of nine distinct polyalkylated furan natural products belonging to different classes, namely the furanoterpenes rosefuran, sesquirosefuran, and mikanifuran; the marine natural products plakorsins A, B, and D and plakorsin D methyl ester; and the furan fatty acids 3D5 and hydromumiamicin.

Palladium-catalysed regio- And stereoselective arylative substitution of γ,δ-epoxy-α,β-unsaturated esters and amides by sodium tetraaryl borates

Palladium-catalysed reactions of γ,δ-epoxy-α,β-unsaturated esters and amides with NaBAr4 reagents proceeded regio- and stereoselectively, producing allylic homoallyl alcohols with aryl-substituents in the allylic position for a wide range of substrates. A

Intramolecular Diels-Alder Approaches to the Decalin Core of Verongidolide: The Origin of the exo-Selectivity, a DFT Analysis

Verongidolide is a natural macrolactone recently isolated from a New Caledonia sponge, Verongidolae. The structure of this natural product is similar to the structure of superstolides, also isolated from a New Caledonian sponge, Neosiphonia superstes. From a biological point of view, verongidolide and superstolides A and B present potent cytotoxicity against human oral carcinoma KB (0.3 nM). By comparing the 1H NMR chemical shifts as well as the coupling constants, we conclude that verongidolide possesses a cis-decalin core and we hypothesize that the relative configuration of the cis-decalin core is similar to the one of superstolide A. To verify this hypothesis, intramolecular and transannular Diels-Alder reactions were attempted to construct the decalin core. Unexpectedly, the selectivity of the Diels-Alder reactions was exo and an in-depth DFT calculation of the key reaction mechanism was achieved in order to understand the factors controlling this unexpected selectivity.

SYNTHESIS OF DISORAZOLES AND ANALOGS THEREOF AS POTENT ANTICANCER AGENTS

In one aspect, the present disclosure provides disorazole analogs of the formula: Formula (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, drug conjugates with cell targeting moieties of the compounds are also provided.

Flow synthesis of (3R)- and (3S)-(E)-1-iodohexa-1,5-dien-3-ol: Chiral building blocks for natural product synthesis

A concise procedure to prepare optically active (3R)- and (3S)-(E)-1-iodohexa-1,5-dien-3-ol was developed. Ethyl (E)-3-iodoacrylate was converted to racemic (E)-1-iodohexa-1,5-dien-3-ol under flow and batch conditions via successive half reduction followed by Grignard reaction. Kinetic resolution of the racemic alcohol was achieved under flow conditions by using lipase packed in a column to afford (3S)-(E)-1-iodohexa-1,5-dien-3-ol and corresponding (3R)-acetate. Removal of the acetyl group was also carried out under flow conditions by using ion exchange resin packed in a column and (3R)-(E)-1-iodohexa-1,5-dien-3-ol was obtained after simple evaporation of the eluent.

Intramolecular cascade rearrangements of enynamine derived ketenimines: Access to acyclic and cyclic amidines

Copper-catalyzed reaction of enynamines with sulfonylazides provides acyclic and cyclic amidines. Nucleophilic addition of the tethered amino group on the in situ generated ketenimine forms a six-membered cyclic zwitterionic intermediate which facilitates

Enantioselective Allylation of β-Haloacrylaldehydes: Formal Total Syntheses of Pteroenone and Antillatoxin

A comparative study of the catalytic allylations and crotylations of (E)- and (Z)-haloacrylaldehydes by Lewis bases (chiral N,N′-dioxides) and Br?nsted acids (chiral phosphoric acids) was undertaken. The reactions proceeded with high enantio- and diastereoselectivities with slightly better asymmetric induction observed in the case of N,N′-dioxide catalysis. The formed enantioenriched chiral unsaturated haloalcohols could be considered general building blocks, as they could be used in the syntheses of more complex natural products possessing substituted 1,3-diene fragments. This was exemplified by the formal total syntheses of pteronenone and antillatoxin. A comparative study of allylations and crotylations of (E)- and (Z)-haloacrylaldehydes is undertaken under Lewis base and Br?nsted acid catalysis. The reactions proceed in both cases with high enantio- and diastereoselectivities. The formed chiral unsaturated haloalcohols can be considered as general building blocks, as exemplified by the formal total syntheses of pteronenone and antillatoxin; HBPin = pinacolborane.

ANTIDIABETIC COMPOUNDS

Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.