title: A concise synthesis of tubuphenylalanine and epi-tubuphenylalanine via a diastereoselective Mukaiyama aldol reaction of silyl ketene acetal.
abstract: We have developed a straightforward and auxiliary-free synthetic route towards tBu-tubuphenylalanine (tBu-Tup) and tBu-epi-tubuphenylalanine (tBu-epi-Tup), which are the key components of tubulysins and their analogs. A Lewis acid-mediated diastereoselective Mukaiyama aldol reaction using silyl ketene acetal and N-Boc-L-phenylalaninal provided γ-amino-β-hydroxyl-α-methyl esters, which were deoxygenated to γ-amino-α-methyl esters under Barton-McCombie deoxygenation conditions. Notably, the desired tBu-Tup and tBu-epi-Tup were obtained in good overall yields in four steps.
authors.affiliation: College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Republic of Korea. ryuj@ewha.ac.kr.
authors.forename: Yunjeong
authors.initials: Y
authors.lastname: Park
authors.forename: Mikyung
authors.initials: M
authors.lastname: Sim
authors.forename: Tong-Shin
authors.initials: TS
authors.lastname: Chang
authors.forename: Jae-Sang
authors.initials: JS
authors.lastname: Ryu
mesh_terms: D000080:Acetals / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D024322:Amino Acids, Aromatic / Q000138:chemical synthesis*; D005030:Ethylenes / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D012821:Silanes / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000080:Acetals; D000447:Aldehydes; D024322:Amino Acids, Aromatic; D005030:Ethylenes; D007659:Ketones; D012821:Silanes; C116609:3-hydroxybutanal; C008223:ketene