Darstellung und Stereochemie von 3‐(α‐Hydroxybenzyl)‐1,4‐diphenyl‐2‐azetidinonen

Abstract

Die Aldol-Addition von Benzaldehyden an 1,4-Diphenyl-2-azetidinone 1 in Gegenwart von Lithiumdiisopropylamid fiihrt in guten Ausbeuten und mit hoher Diastereoselektivitat an drei Zentren zu den Titelverbindungen rnit aS+,3S*,4RC-Konfiguration. Die gleiche Konfiguration wird bei Umsetzungen von 1 rnit Acetaldehyd bevorzugt gebildet. Synthesis and Stereochemistry of 3-(a-Hydroxybenzyl)-1,4-diphenyl-2-azetidinonesAldol reaction between benzaldehydes and 1,4-diphenyl-2-azetidinones 1 catalyzed by lithium diisopropylamide results in formation of the title compounds. The reactions give satisfactory yields and high diastereoselectivity at three centres in forming the aS*,3S*,4R * configuration.The same configuration is preponderant if acetaldehyde is reacted with 1.

β-Lactam Estrogen Receptor Antagonists and a Dual-Targeting Estrogen Receptor/Tubulin Ligand

“…Tubulin is an αβ heterodimeric protein and is the main constituent of microtubules, which are essential to the mitotic division of cells. 36 which contains a basic side-chain similar to known SERMs (Scheme 3). 19 There are a number of potential advantages for designed multiple ligands, for example, improved efficacy, less incidence of side effects and a lower risk of drug-drug interactions.…”

“…The introduction of the required substituent at the C-3 position was achieved with an aldol type reaction of a suitable phenolic aldehyde to produce the α-(hydroxyaryl)methyl group at the C-3 position of the β-lactam. 36 Reaction of 16, 17, and 18 with 4-hydroxybenzaldehyde afforded the products 26, 27, and 29, respectively (Scheme 3). Debenzylation of 27 yielded the required triphenolic product 28.…”

“…A structurally related group of compounds containing the common β-lactam core structure substituted with aryl rings at the N-1 and C-4 positions, together with the arylhydroxymethyl substituent at C-3, were also prepared to provide further insight on the structural requirements of the β-lactam scaffold for ER binding activity. The introduction of the required substituent at the C-3 position was achieved with an aldol type reaction of a suitable phenolic aldehyde to produce the α-(hydroxyaryl)­methyl group at the C-3 position of the β-lactam . Reaction of 16 , 17 , and 18 with 4-hydroxybenzaldehyde afforded the products 26 , 27 , and 29 , respectively (Scheme ).…”

Lithium Diisopropylamide

“…ketones (eqs 1 and 3), 19,20 αamino ketones, 21 ω-bromo ketones (eq 4), 10 imines (eqs 6 and 7), 22-24 imino ethers (eq 8), 25 carboxylic acids (eq 9), 26 carboxylic esters, 27 lactones, 28 amides, 29 lactams, 30 imides, 31 and nitriles 32 which may be alkylated or used in aldol condensations. Enolates of methyl ketones may be O-alkylated with Diethyl Phosphorochloridate to give enol phosphates which, upon β-elimination, afford terminal alkynes in high yields (eq 5).…”