Xylapyrrosides A and B, two rare sugar-morpholine spiroketal pyrrole-derived alkaloids from Xylaria nigripes: isolation, complete structure elucidation, and total syntheses

Stereocontrolled Synthesis of Spiroketals: An Engine for Chemical and Biological Discovery

“…This novel family of naturally-occurring alkaloids includes both furanose and pyranose isomeric forms, as well as both epimeric α- and β-configurations at the anomeric carbon (Figure 13). 31 These natural products were isolated from a variety of different plant species ( Acorus tatarinowii , Brassica campestris , and Capparis spinosa , Shensong Yangxin capsules), as well as a fungus ( Xylaria nigripes ), all of which have been used in traditional Chinese medicines for the treatment of a variety of diseases. Notably, the acortatarins exhibit significant antioxidant activity against hyperglycemia-induced oxidative stress in kidney cells, 31a and similarly, the xylapyrrosides protect against peroxide-induced cytotoxicity in vascular smooth muscle cells.…”

“…31 These natural products were isolated from a variety of different plant species ( Acorus tatarinowii , Brassica campestris , and Capparis spinosa , Shensong Yangxin capsules), as well as a fungus ( Xylaria nigripes ), all of which have been used in traditional Chinese medicines for the treatment of a variety of diseases. Notably, the acortatarins exhibit significant antioxidant activity against hyperglycemia-induced oxidative stress in kidney cells, 31a and similarly, the xylapyrrosides protect against peroxide-induced cytotoxicity in vascular smooth muscle cells. 31f These antioxidant effects suggest that the pyrrolomorpholine spiroketals may have therapeutic potential for the treatment of diabetic nephropathy and other oxidative stress-related pathologies.…”

“…Notably, the acortatarins exhibit significant antioxidant activity against hyperglycemia-induced oxidative stress in kidney cells, 31a and similarly, the xylapyrrosides protect against peroxide-induced cytotoxicity in vascular smooth muscle cells. 31f These antioxidant effects suggest that the pyrrolomorpholine spiroketals may have therapeutic potential for the treatment of diabetic nephropathy and other oxidative stress-related pathologies. However, due to the extremely limited quantities available from the natural sources, efficient synthetic access is needed for comprehensive biological studies.…”

“…Accordingly, this family of natural products has attracted considerable attention from the synthetic community. 31b,f,32 We envisioned that we might access the natural products and analogues efficiently using our glycal epoxide rubric and related glycal-based approaches.…”

“…Interestingly, however, reductive spirocyclization with NaBH 3 CN under acidic conditions yielded the corresponding C1-epimeric α-spiroketal as a single diastereomer. Desilylation of β-spiroketal 82 provided acortatarin B ( 73 ) while C1- epi -acortatarin B ( 71 , later isolated as the natural product shensongine C 31e ) was accessed by desilylation of the corresponding protected α-spiroketal (not shown).…”