TY - JOUR
T1 - Total Synthesis and Structure Confirmation of trans-Anhydromevalonate-5-phosphate, a Key Biosynthetic Intermediate of the Archaeal Mevalonate Pathway
AU - Yasuno, Yoko
AU - Nakayama, Atsushi
AU - Saito, Kai
AU - Kitsuwa, Kohei
AU - Okamura, Hironori
AU - Komeyama, Mutsumi
AU - Hemmi, Hisashi
AU - Shinada, Tetsuro
N1 - Funding Information:
This work was financially supported by JSPS KAKENHI (JP19H04661, JP19H04651, JP20K09396, and JP21K14629), the OCU ‘Think globally, act locally’ Research Grant for Young Scientists 2021 through the hometown donation fund of Osaka City, the Uehara Memorial Foundation for A.N., and the Sasakawa Scientific Research Grant from The Japan Science Society for H.O.
Publisher Copyright:
© 2021 American Chemical Society and American Society of Pharmacognosy.
PY - 2021/10/22
Y1 - 2021/10/22
N2 - The mevalonate pathway is an upstream terpenoid biosynthetic route of terpenoids for providing the two five-carbon units, dimethylallyl diphosphate, and isopentenyl diphosphate. Recently, trans-anhydromevalonate-5-phosphate (tAHMP) was isolated as a new biosynthetic intermediate of the archaeal mevalonate pathway. In this study, we would like to report the first synthesis of tAHMP and its enzymatic transformation using one of the key enzymes, mevalonate-5-phosphate dehydratase from a hyperthermophilic archaeon, Aeropyrum pernix. Starting from methyl tetrolate, a Cu-catalyzed allylation provided an E-trisubstituted olefin in a stereoselective manner. The resulting E-olefin was transformed to tAHMP by cleavage of the olefin and phosphorylation. The structure of the synthetic tAHMP was unambiguously determined by NOESY analysis.
AB - The mevalonate pathway is an upstream terpenoid biosynthetic route of terpenoids for providing the two five-carbon units, dimethylallyl diphosphate, and isopentenyl diphosphate. Recently, trans-anhydromevalonate-5-phosphate (tAHMP) was isolated as a new biosynthetic intermediate of the archaeal mevalonate pathway. In this study, we would like to report the first synthesis of tAHMP and its enzymatic transformation using one of the key enzymes, mevalonate-5-phosphate dehydratase from a hyperthermophilic archaeon, Aeropyrum pernix. Starting from methyl tetrolate, a Cu-catalyzed allylation provided an E-trisubstituted olefin in a stereoselective manner. The resulting E-olefin was transformed to tAHMP by cleavage of the olefin and phosphorylation. The structure of the synthetic tAHMP was unambiguously determined by NOESY analysis.
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U2 - 10.1021/acs.jnatprod.1c00615
DO - 10.1021/acs.jnatprod.1c00615
M3 - Article
C2 - 34597517
AN - SCOPUS:85117186328
SN - 0163-3864
VL - 84
SP - 2749
EP - 2754
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 10
ER -