Bridged to Fused Ring Interchange. Methodology for the Construction of Fused Cycloheptanes and Cyclooctanes. Total Syntheses of Ledol, Ledene, and Compressanolide

Abstract

The type two intramolecular Diels-Alder reaction (T2IMDA) is an efficient method for the formation of medium rings. The methodology is particularly effective for the construction of seven- and eight-membered rings. A strategy for the synthesis of functionalized cycloheptanes and cyclooctanes has been developed that involves a bridged to fused ring interchange. The T2IMDA provides a synthesis for rigid bridged bicyclic molecules that can be stereoselectively elaborated before ozonolysis of the bridgehead double bond. Following oxidative cleavage, aldol condensation provides fused bicyclic ring systems that otherwise are difficult to synthesize. This methodology is amenable to the synthesis of terpene natural products. This is demonstrated here through total syntheses of (+/-)-ledol and (+/-)-ledene and a formal synthesis of (+/-)-compressanolide.

Ruthenium–Lewis Acid Catalyzed Asymmetric Diels–Alder Reactions between Dienes and α,β‐Unsaturated Ketones

“…Product 31 had a negative [a] value even though its CD spectrum more closely resembles 30 than 22; thus, we used a similar analogy as Corey [20] (for 22 by comparing it to 10) for assigning the S absolute configuration to 31. Intramolecular Diels-Alder reaction: The racemic version of the intramolecular Diels-Alder reaction shown in Scheme 4 was previously reported by Shea and co-workers [35] and substrate 32 can be prepared in three steps. Shea examined several related intramolecular Diels-Alder reactions.…”

HRGC/FID and HRGC/MSD Analysis of the Secondary Metabolites Obtained by Different Extraction Methods fromLepechinia schiedeana, andin Vitro Evaluation of Its Antioxidant Activity

“…reported by Gwaltney and co-workers [22]. Since so far there are no reports on 2D NMR data on ledol, we present here for completeness the group assignments and the chemical shifts Other compounds found in high proportion were d-3-carene (15.78 -22.01%), b-pinene (4.30 -8.04%), a-terpinene (3.65 -6.14%), and a-farnesene (2.10 -2.81%).…”

“…Thus, macerated Lepechinia plant demonstrated activity in the protection of unsaturated fatty acids from their oxidative degradation. Based on these results we are currently extending our study of Lepechinia in order to characterize more thoroughly its diterpene and phytosterol fractions, as these fractions in rosemary and sage (Labiatae family) extracts possess strong antioxidant activity [22,23].…”

New ent-Verticillane Diterpenoids from the Japanese Liverwort Jackiella javanica

“…A combination of chromatography on silica gel, Sephadex LH-20 and preparative HPLC of the ether extract of J. javanica afforded three new ent-verticillanes 10-12 as well as known sesquiterpenoids, ent-ledene (13), 9) ent-4,10-aromadendrandiol (14), 10) (1R,7R)-germacra-4(15),5E,10(14)-trien-1-ol (15) 4) and ent-11-hydroxy-5-guaien (16), 11) and a diterpene hydrocarbon, ent-exo-verticillene (17). [12][13][14] The structures of the known compounds were determined by comparison of authentic 1 H-and 13 C-NMR spectra and/or reference data.…”