Homo-aro-cholestane glycosides from Ypsilandra thibetica modulate the expansion of human cord blood hematopoietic stem and progenitor cells.

A chemical investigation of Ypsilandra thibetica led to the isolation of ten previously undescribed homo-aro-cholestane glycosides, aroypsilandrosides A-J (1-10), along with the known analogue 11 and its aglycone 12. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, chemical methods, and single-crystal X-ray diffraction. Notably, aroypsilandroside A (1) is an unprecedented B-abeo-homo-aro-cholestane glycoside featuring a 6/5/6/5/6 fused ring system. Aroypsilandrosides B-D (2-4) possess a rare Δ4 double bond with a hydroxyl or carbonyl group at C-6, whereas aroypsilandrosides H-J (8-10) represent the second report of naturally occurring homo-aro-cholestane glycosides bearing a carboxylated aromatic E-ring. Compounds 1-8, 11, and 12 were evaluated for their effects on the ex vivo expansion of human cord blood (CB) CD34+ hematopoietic stem and progenitor cells (HSPCs). Compound 11 markedly expanded hematopoietic stem cells (HSCs, 7.6-fold) and multipotent progenitors (MPPs, 29.2-fold), representing the most potent HSC and MPP expansion activity reported to date among naturally occurring compounds in this assay. Furthermore, structure-activity relationship analysis identified the bidesmosidic homo-aro-cholest-5-ene glycoside skeleton as a new chemotype for HSPC expansion. These findings establish homo-aro-cholestane glycosides as a promising class of modulators for ex vivo expansion of human CB HSPCs.