title: Gram-Scale Laboratory Synthesis of UM171, a Potent Agonist of Human Hematopoietic Stem Cell Self-Renewal.
abstract: A short economic synthesis of pyrimidoindole derivative UM171, a potent agonist for the ex vivo expansion of hematopoietic stem cells, has been developed in this work. A unique [3,3]-sigmatropic rearrangement upon a hydroxamic precursor followed by base-promoted cyclization was successfully applied as the key step, furnishing the fully functionalized indole nucleus. The current synthesis is not only capable of affording UM171 in gram quantities but also offers great flexibility in late-stage diversification. Three new analogues of UM171 were synthesized accordingly in excellent yields using the common indole-carboxamide intermediate.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road, Shanghai 200032, China.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Ali
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road, Shanghai 200032, China.
authors.forename: Shun-Ming
authors.initials: SM
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road, Shanghai 200032, China.
authors.forename: Zhu-Jun
authors.initials: ZJ
authors.lastname: Yao
mesh_terms: D000066673:Cell Self Renewal / Q000187:drug effects*; D003500:Cyclization; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013057:Spectrum Analysis
chemical_list: D007211:Indoles; D011743:Pyrimidines; C000592665:UM171 compound