Exploration of ω-side chain addition strategies for the syntheses of isocarbacyclin and 15R-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin

Abstract

We describe alternative access to prostacyclin analogues by means of two omega-side chain addition strategies: Grignard reagent addition to an alpha,beta-unsaturated Weinreb amide, followed by diastereoselective reduction of the corresponding enone system, and implementation of Seebach's alkylation chemistry. These strategies have led to the syntheses of biologically active prostacyclin analogues isocarbacyclin and 15R- 16-(m-tolyl)- 17,18,19,20-tetranorisocarbacyclin (15R-TIC), with modest to excellent diastereoselectivity.

Recent Developments in the Synthesis of Prostaglandins and Analogues

“…Another route was proposed recently for the preparation of this compound, as described in Scheme . The intermediate 659 , protected with the bulky trityl group, which was obtained in a few steps from know bicyclic intermediates, was deprotonated with a high regioselectivity (16:1), affording, after trapping with PhNTf 2 , the derivative 660 .…”

“…The lower chain was introduced through a Julia−Kociencski olefination procedure starting from 662 . Final functional group transformations were routine to prepare the target molecule 658 144a. Another recent alternative was the use of the Weinreb amide derivative 664 , easily accessible from 662 .…”

DBU-catalyzed diastereoselective 1,3-dipolar [3+2] cycloaddition of trifluoroethyl amine-derived isatin ketimines with chalcones: synthesis of 5′-CF3-substituted 3,2′-pyrrolidinyl spirooxindoles

“…4,5 As we know, chalcones are a well-studied group of naturally occurring aromatic ketones with biological properties including anti-inflammatory and anti-cancer. 6 Additionally, owing to their facile synthetic accessibility and ɑ,β-unsaturated carbonyl conjugated system containing two electrophilic centers, they are frequently used as valuable intermediates for the formation of heterocycles, particularly five- and six-membered heterocyclic molecules. 7 Considering the importance of spirooxindoles, fluorine compounds, and chalcones, we hypothesized that their integration could augment the bioactivities.…”

Exploring the Antioxidant Potency of New Naphthalene‐Based Chalcone Derivatives: Design, Synthesis, Antioxidant Evaluation, Docking Study, DFT Calculations

“…Chalcones, (E)-1,3-diaryl-2-propen-1-ones, have attracted much attention in the field of medicinal chemistry due to their facile synthesis, high reactivity, and promising pharmacological activities. [3,4] They represent a group of natural products that belong to the flavonoid family, and can exist in various flowers, fruits, vegetables. Several synthetic methods have been reported for the preparation of chalcones, such as Claisen-Schmidt reactions, Heck coupling, Suzuki-Miyaura coupling, and Witting reactions.…”