Synthesis and Biological Activity of New 3-Hydroxy-3-methylglutaryl-CoA Synthase Inhibitors: 2-Oxetanones with a meta-Substituent on the Benzene Ring in the Side Chain.

The biosynthesis of steroids and triterpenoids

“…9 Analogues of acetyl-CoA have been synthesised for studies of a variety of biosynthetic pathways, including the terpenoid pathway, which utilise this precursor. 10,11 Syntheses and activities of a number of HMGS inhibitors have been described, including the known natural product -lactone 1233A (13) 12 (an irreversible inhibitor also referred to as L-659,699), 13,14 its structural analogues [15][16][17][18][19][20][21] and the new hypolipidemic compound lifibrol (K12.148). 22,23 A fungalderived -lactone incorporating a long alkyl chain is also Scheme 2 Biosynthesis of squalene epoxide in eukaryotes; Enzymes: i, AACT; ii, HMGS; iii, HMGR; iv, MVAK; v, MVAPK; vi, MPD; vii, IPP isomerase; viii, FPS; ix, SQS; x, SE.…”

A Synthesis of the Hypocholesterolemic Agent 1233A Via Asymmetric [2 + 2] Cycloaddition

“…15 Omura has described a number of highly active simpler analogues. [16][17][18][19][20] We now report a concise asymmetric synthesis of 1233A (1) from three fragments plus CO 2 (Scheme 1) in which all three stereogenic centres are secured by asymmetric methods.…”

Platform approach to diversification: bio-based methyl coumalate to functionalized aromatics via a Diels-Alder strategy

“…Selected variations on the Diels-Alder reaction. 25,[28][29][30] Scheme 2. First-reported Diels-Alder reaction between the 2-pyrone methyl coumalate (13) and maleic anhydride (14).…”

“…Aromatic compound 24b has already proven beneficial as one of the primary starting materials for a cholesterol inhibitor 33 (Figure 2). 30 In general, preparations of 24b entail protecting the corresponding alcohol which is only commercially available from very few suppliers and is a simple functional group manipulation which does not construct the aromatic The second carbonyl functionality could also be achieved by converting 2,4-pentanedione to 4-methoxypent-3-en-2-one 23da by an acid-catalyzed procedure. 32 Surprisingly, exclusive formation of 24d was observed when 23da was subjected to the established Diels-Alder conditions, which was confirmed by 1 H NMR data with a singlet at 3.77 ppm for the methylene protons adjacent to the aromatic ring.…”

“…Since its discovery in 1928, 24 the reaction has been regularly incorporated into numerous syntheses to construct sophisticated frameworks in academia 25,26 and industry. 27 Further advances have yielded variations from hetero-Diels-Alder 28 to transannular Diels-Alder 29 to inverse electrondemand Diels-Alder (IEDDA) 30,31 reactions as depicted in Scheme 1 which are a testament to its scope and utility. A critical aspect in controlling the regiochemistry of the reaction involves effectively matching an electron-deficient diene with an electronrich dienophile for optimal orbital overlap in the IEDDA reaction which is governed by the electronics of the Diels-Alder partners.…”