123185-87-5

Upstream product

• 123185-85-3 tert-butyl cis-3,5-dihydroxy-7-phenylhept-6-enoate 
• 1694-31-1 tert-butyl acetoacetate 
• 123185-86-4 t-butyl (3S^*,5R^*,6E)-7-phenyl-3,5-isopropylidenedioxy-6-heptenoate 

Downstream Products

• 118845-49-1 trans-6-<4,4-bis(4-fluorophenyl)-3-(1-methyl-1H-tetrazol-5-yl)-1,3-butadienyl>tetrahydro-4-hydroxy-2H-pyran-2-one 
• 118918-05-1 trans-(4R,6S)-6-[4,4-bis(4-fluorophenyl)-3-(1-methyl-1H-tetrazol-5-yl)-1,3-butadienyl]-tetrahydro-4-hydroxy-2H-pyran-2-one 
• 123284-04-8 (4S,6R)-6-[(E)-4,4-Bis-(4-fluoro-phenyl)-3-(1-methyl-1H-tetrazol-5-yl)-buta-1,3-dienyl]-4-hydroxy-tetrahydro-pyran-2-one 

Relevant academic research and scientific papers

A 2 - ((4R, 6S) - 6-formyl -2,2-di-substituted -1,3-dioxane-4-yl) ethyl ester preparation method

The invention relates to a simple and convenient preparation method of 2-((4R,6S)-6-formyl-2,2-disubstituted-1,3-dioxane-4-yl)acetate. The 2-((4R,6S)-6-formyl-2,2-disubstituted-1,3-dioxane-4-yl)acetate has a structure shown in a formula I. The preparation method comprises the following steps: by taking butadiene and 3,3-dialkyloxypropionate or 3-alkyloxyacrylate as raw materials, cyclizing under the catalysis of lewis acid to substitute benzaldehyde to form cyclic protection, then hydrolyzing and performing cyclization reaction with corresponding aldehyde (ketone) or dimethylacetal and diethylacetal thereof to prepare the 2-((4R,6S)-6-vinyl-2,2-disubstituted-1,3-dioxane-4-yl)acetate, and then preparing I through three-step reaction of vinyl ozonization. The preparation method is easily available in raw materials, and short in reaction process, a chiral center is constructed by utilizing the stabilization form of an equatorial bond of a hexatomic ring chair type structure, a flammable and combustible asymmetric reducer is not used, and the preparation method is simple and convenient and environment-friendly, and suitable for industrial production of chiral side chains of statins.

Synthesis, biological profile, and quantitative structure - Activity relationship of a series of novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors

A series of 9,9-bis(4-fluorophenyl)-3,5-dihydroxy-8-(alkyltetrazol-5-yl)-6,8-nonad ienoic acid derivatives 1 were synthesized and found to inhibit competitively the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The analogues having 1N-methyltetrazol-5-yl attached to the C8-position (3a, 4a, R1 = R2 = F) are the most active in suppressing cholesterol biosynthesis in both in vitro and in vivo models: the IC50 for the chiral form of 3a is 19 nM, K(i) = 4.3 x 10-9 M when K(m) for HMG-CoA is 28 x 10-6 M; the ED50 (oral) value corresponding to the lactone derivative (4a, BMY 22089) is approximately 0.1 mg/kg. Further, BMY 21950 is nearly 2 orders of magnitude more active in parenchymal hepatocytes, from which most of the serum cholesterol originates, than in other cell preparations (such as spleen, testes, ileum, adrenal, and ocular lens epithelial cells; Table III). This apparent tissue specificity may be highly beneficial since the blocking of cholesterol biosynthesis in other vital organs could eventually lead to undesirable side effects. In addition to the chemical synthesis and biological evaluation, a theoretical study aimed at relating the HMG-CoA reductase inhibitory potency to the three-dimensional structure of the inhibitors was undertaken. With a combination of molecular mapping and 3D-QSAR techniques, it was possible to determine a logical candidate for the conformation of the bound inhibitor and to quantitatively relate inhibitory potency to the shape and size of both the binding site and the C8-substituent.