Synthesis of ertugliflozin from D-glucose

被引：5

作者：

Triantakonstanti, Virginia V. ^{[1
]}

Andreou, Thanos ^{[2
]}

Koftis, Theoharis V. ^{[2
]}

Gallos, John K. ^{[1
]}

机构：

[1] Aristotle Univ Thessaloniki, Dept Chem, Thessaloniki 54124, Greece

[2] Pharmathen Ind SA, 9th Km Thermi Thessaloniki, Thessaloniki 57001, Greece

来源：

TETRAHEDRON LETTERS | 2019年 / 60卷 / 14期

关键词：

Ertugliflozin; D-Glucose; Grignard reaction; Benzylic oxidation; SGLT2; inhibitors; SELECTIVITY; SILYLATION; REACTIVITY; ALCOHOLS; ROUTE;

D O I：

10.1016/j.tetlet.2019.03.009

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A new synthesis of ertugliflozin from n-glucose in 7% overall yield is reported. The reaction sequence involves conversion of n-glucose to a fully protected open chain n-glucose aldehyde in 4 steps, further installation of the aglycon group by a Grignard reaction, introduction of the hydroxymethyl group by a sequential oxidation/aldol reaction/Canizzarro reduction, and finally benzylic oxidation and global deprotection. (C) 2019 Elsevier Ltd. All rights reserved.

引用

页码：994 / 996

页数：3

共 21 条

[1] Synthetic Strategies toward SGLT2 Inhibitors [J].

Aguillon, Anderson R. ;

Mascarello, Alessandra ;

Segretti, Natanael D. ;

de Azevedo, Hatylas F. Z. ;

Guimaraes, Cristiano R. W. ;

Miranda, Leandro S. M. ;

de Souza, Rodrigo O. M. A. .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2018, 22 (04) :467-488

[2]

[Anonymous], 1999, Protective Groups in Organic Synthesis

[3]

[Anonymous], 2021, IDF Diabetes Atlas

[4] Development of an Early-Phase Bulk Enabling Route to Sodium-Dependent Glucose Cotransporter 2 Inhibitor Ertugliflozin [J].

Bernhardson, David ;

Brandt, Thomas A. ;

Hulford, Catherine A. ;

Lehner, Richard S. ;

Preston, Brian R. ;

Price, Kristin ;

Sagal, John F. ;

St Pierre, Michael J. ;

Thompson, Peter H. ;

Thuma, Benjamin .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2014, 18 (01) :57-65

[5] Preparation of α- and β-D-glucoseptanose pentaacetates [J].

Bhadbhade, Mohan ;

Craig, Donald C. ;

Ng, Clarence J. ;

Odier, Leon ;

Stevens, John D. .

CARBOHYDRATE RESEARCH, 2012, 353 :86-91

[6] Silyl-protective groups influencing the reactivity and selectivity in glycosylations [J].

Bols, Mikael ;

Pedersen, Christian Marcus .

BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, 2017, 13 :93-105

[7] Commercial Route Research and Development for SGLT2 Inhibitor Candidate Ertugliflozin [J].

Bowles, Paul ;

Brenek, Steven J. ;

Caron, Stephane ;

Do, Nga M. ;

Drexler, Michele T. ;

Duan, Shengquan ;

Dube, Pascal ;

Hansen, Eric C. ;

Jones, Brian P. ;

Jones, Kris N. ;

Ljubicic, Tomislav A. ;

Makowski, Teresa W. ;

Mustakis, Jason ;

Nelson, Jade D. ;

Olivier, Mark ;

Peng, Zhihui ;

Perfect, Handi H. ;

Place, David W. ;

Ragan, John A. ;

Salisbury, John J. ;

Stanchina, Corey L. ;

Vanderplas, Brian C. ;

Webster, Mark E. ;

Weekly, R. Matt .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2014, 18 (01) :66-81

[8] INTRAMOLECULAR REACTIONS OF COMPOUNDS DERIVED FROM SUGARS .3. HIGH DIASTEREOSELECTION IN THE INTRAMOLECULAR DIELS-ALDER REACTION OF SUGAR BASED 1,7(E,Z),9-DECATRIENES [J].

HERCZEGH, P ;

ZSELY, M ;

SZILAGYI, L ;

DINYA, Z ;

BOGNAR, R .

TETRAHEDRON, 1989, 45 (18) :5995-6002

[9]

Kocienski P.J., 1994, PROTECTING GROUPS

[10]

Mascitti V., 2010, [No title captured], Patent No. [W010023594, 10023594]

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