Cyclopeptide alkaloids: chemistry and biology

Abstract

Recent progress in the synthesis and investigation of the biological activities of cyclopeptide alkaloids is reviewed. New strategies have been devised to overcome some of the synthetic challenges inherent in the formation of strained paracyclophanes. However, issues remain which offer opportunities for the application of catalytic enantioselective organometallic reactions. Members of this class of natural products have been isolated from various parts of a wide variety of plants and researchers will likely continue to show great interest in their formation and function. The biological properties of certain members of this class warrant further investigation. To gain additional insight into these areas, continuing development of synthetic methodology will be essential.

Stereoselective Hydrogenation ofCCBonds: Application to Drug and Natural Product Synthesis

“…231 Adamczyk and co-workers set out to develop a straightforward access to enantioenriched (S)-(À)-acromelobinic 232 and (S)-(À)-acromelobic 233 acids to achieve elaboration of asymmetric hydrogenation of dehydroamino acid derivatives 145 and 147 (Scheme 29.10). 234 The dehydroamino acid derivative 145 was hydrogenated in the pres- Cyclopeptide alkaloids 235,236 belong to a class of natural products widely distributed among plants of the Rhamnaceae family, 237 but their occurrence has also been confirmed in representatives of Celastraceae, 238 antifungal, sedative, and antiplasmodial. 239 Both abyssenine A and murconine E were isolated from the roots and stem bark of several Zizyphus-type Rhamnaceae.…”

Biomimetic Synthesis of Azole‐ and Aryl‐Peptide Alkaloids

“…No genuine biomimetic approach to the macrocyclization according to those already proposed (Scheme 9.12) has been established thus far. Ring closure as the key step in each of these synthetic routes has been accomplished at different positions of the molecular scaffold (Figure 9.9) [61]. Schmidt et al have introduced a macrolactamization approach based on the activation of a carboxyl-group as a pentafluorophenyl ester, which was further applied to the synthesis of several cyclopeptide alkaloids (Schmidt et al [62][63][64][65][66][67][68][69], Joullié et al [70][71][72][73][74][75][76], Han et al [77][78][79]).…”

Rapid Synthesis of Cyclopeptide Alkaloid‐Like para‐Cyclophanes by Combined Use of Ugi‐4CR and Intramolecular SNAr Reaction

“…Among them, the 14-membered para-cyclophanes such as sanjoinine G1 (1), sanjoinine A (2) and mauritine B (3) (Figure 1) with an endo aryl -alkyl ether bond represent the largest subgroup and have been the main research focus in the area [2,3]. On the other hand, non-natural para-cyclophanes with an endo aryl -X -alkyl bond such as aryl -alkyl ether 4 [4], aryl -alkyl amine 5 [5], and aryl -alkyl thioether 6 [6] have been designed and synthesized for targeted biological activity evaluations.…”

“…Interesting biological properties such as sedative, antibacterial and antifungal activities have been found for members of cyclopeptide alkaloids [1,2]. The para-cyclophane structure has been also used with success as a key structural element in the design of enzyme inhibitors [4,7].…”

“…Various synthetic strategies have been consequently developed for the preparation of this type of macrocycle. Among them, the macrolactamization [1,2] and intramolecular S N Ar-based cycloetherification [8] have been successfully applied to the synthesis of strained 14-membered natural cyclopeptide alkaloids [2], whereas intramolecular S N 2 displacement has been implemented for the synthesis of non-strained para-cyclophanes [4,7].…”