Total Synthesis of Archaeal Dolichol
<none>
Programme Social programme Plenary speakers Keynote speakers 1st EuroCarb Young Researcher (ECYR) Workshop CarboMet Workshop Mini symposium: Glycobiology at the LUMC and beyond Favourites/Agenda
Social programme
Plenary speakers
Keynote speakers
1st EuroCarb Young Researcher (ECYR) Workshop
CarboMet Workshop
Mini symposium: Glycobiology at the LUMC and beyond
Favourites/Agenda
Photos
Venue & Travel Venue Accommodation City of Leiden Travel directions
Venue
Accommodation
City of Leiden
Travel directions
Committees
Home
Total Synthesis of Archaeal Dolichol
Kohtaro Hirao 1 , Yoshiyuki Manabe 1,2 , Risako Ono 1 , Koichi Fukase 1,2
1 Graduate School of Science, Osaka University, Toyonaka-shi, Osaka, Japan, 2 Project Research Center for Fundamental Sciences, Osaka University, Toyonaka-shi, Osaka, Japan
Archaea forms one domain in a phylogenetic tree of biological evolution along with eukaryotes and eubacteria. N-Glycosylations are one of the most abundant posttranslational modifications in archaea as well as eukaryotes. Dolichol is used as a carrier lipid of N-glycans in their biosynthesis. To investigate the transglycosylation process in hyperthermophilic archaea, Thermococcus kodakarensis, we herein synthesized dolichol 8.
The first important point is that the scalable synthesis of key intermediate 3, since dolichol 8 consists of repeating structure of Z-isoprene unit. Thus, we investigated Z-selective Wittig reaction using ketone 2 and unstable ylide generated from 1 under kinetically controlled conditions. When the solution of ketone 2 was dropwisely added to the ylide solution at -78 ˚C, 3 was obtained in high yield (table 1, entry 1). However, Z-selectivity was decreased in larger scale owing to the insufficient removal of the reaction heat. We then applied microflow system to achieve the precise reaction temperature control (table 1, entry 2). After mixing the solution of ylide and the solution of 2 in CometX-01 micromixer at -78 ˚C, the resultant solution was stirred for additional 30 mins to give 3 with high Z selectivity (E/Z = 22/1). Scalable synthesis of 3 was then achieved under the continuous flow conditions. The coupling between 4 and 5, both of which were synthesized from 3, was next investigated. When 5 was added to the solution of lithiated 4 with n-BuLi, reproducibility was low owing to the instability of the lithiated 4 (table 2, entry 1). We then applied the Barbier-like protocol to trap generated anion immediately (table 2, entry 2). t-BuOK was added to a mixture of 4 and 5 in DMF at -50 ˚C to afford 6 in high yield (87%) with good reproducibility. After coupling of 6 with 7, containing a saturated moiety, cleavage of the protective group followed by removal of the PhSO2 groups to give dolichol 8.
Synthesis of dolichol 8
Contact eurocarb@eurocarb2019.com for general questions about EUROCARB2019, or codee@eurocarb2019.com for scientific questions.
Leiden University / Leiden Institute of Chemistry lic.leidenuniv.nl
European Carbohydrate Organisation
Congress by Design www.congressbydesign.com