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US 10,696,703 B2Granted
Method for producing eushearlilides
AssigneeTokyo University of Science Foundation
InventorsIsamu Shiina, Takayuki Tonoi
Life of this patent
Estimating the term…
Abstract
Provided are: eushearilides; a method for producing eushearilides; a production intermediate; and a pharmaceutical composition containing eushearilides. By having the Wittig reaction process, Mukaiyama Aldol reaction process and Macrolactonizaion process serve as key processes, eushearilides represented by formula (I) are efficiently produced.
Claims7
The method of manufacturing eushearilides represented by the formula (I), the method comprising the following steps 1 to 10:
- Step 1:
- a step of coupling a compound represented by the formula (I-1):
- wherein P1 represents a protecting group,
- with a compound represented by the formula (I-2):
- wherein R1 represents a hydrogen atom or an optionally substituted hydrocarbon group, wherein the hydrocarbon group is an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkynyl group having 2 to 8 carbon atoms, or an aryl group having 6 to 18 carbon atoms, and wherein the substituent is a hydroxy group, an alkoxycarbonyl group having 1 to 8 carbon atoms in the alkoxy moiety, an amino group, a nitro group, a cyano group, an alkoxy group having 1 to 8 carbon atoms, a carboxy group, or a phosphate group, and P2 represents a protecting group, and X represents a halogen atom,
- in the presence of a base to obtain a compound represented by the formula (I-3):
- wherein R1, P1, and P2 are as defined above;
- Step 2:
- a step of deprotecting the compound represented by the formula (I-3) to obtain a compound represented by the formula (I-4):
- wherein R1 and P2 are as defined above;
- Step 3:
- a step of oxidizing the compound represented by the formula (I-4) to obtain a compound represented by the formula (I-5):
- wherein R1 and P2 are as defined above;
- Step 4:
- a step of subjecting the compound represented by the formula (I-5) to the aldol reaction to obtain a compound represented by the formula (I-6):
- wherein R5 represents a hydrocarbon group, wherein the hydrocarbon group is an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkynyl group having 2 to 8 carbon atoms, or an aryl group having 6 to 18 carbon atoms, and R1 and P2 are as defined above;
- Step 5:
- a step of transesterifying the compound represented by the formula (I-6) to obtain a compound represented by the formula (I-7):
- wherein R1, R5, and P2 are as defined above;
- Step 6:
- a step of protecting, deprotecting the compound represented by the formula (I-7) to obtain a compound represented by the formula (I-8):
- wherein P3 represents a protecting group, and R1 and R5 are as defined above;
- Step 7:
- a step of hydrolyzing the compound represented by the formula (I-8) to obtain a compound represented by the formula (I-9):
- wherein R1 and P3 are as defined above;
- Step 8:
- a step of cyclizing the compound represented by the formula (I-9) to obtain a compound represented by the formula (I-10);
- wherein R1 and P3 are as defined above;
- Step 9:
- a step of deprotecting the compound represented by the formula (I-10) to obtain a compound represented by the formula (I-11):
- wherein R1 is as defined above;
- Step 10:
- a step of allowing the compound represented by the formula (I-11) to react with a phosphorus compound, and then with an amine R2R3R4N to obtain a compound represented by the formula (I):
- wherein R1 is as defined above, and R2, R3, and R4 independently represent a hydrogen atom or an optionally substituted hydrocarbon group, wherein the hydrocarbon group is an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkynyl group having 2 to 8 carbon atoms, or an aryl group having 6 to 18 carbon atoms, and wherein the substituent is a hydroxy group, an alkoxycarbonyl group having 1 to 8 carbon atoms in the alkoxy moiety, an amino group, a nitro group, a cyano group, an alkoxy group having 1 to 8 carbon atoms, a carboxy group, or a phosphate group.
31 more elements
A method of manufacturing eushearilides represented by the formula (Ia), comprising:
- allowing a compound represented by the formula (Ia-11):
- to react with a phosphorus compound, and then with an amine R2R3R4N to obtain the eushearilides represented by the formula (Ia):
- wherein R1, R2, R3, and R4 independently represent a hydrogen atom or an optionally substituted hydrocarbon group, wherein the hydrocarbon group is an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkynyl group having 2 to 8 carbon atoms, or an aryl group having 6 to 18 carbon atoms, and wherein the substituent is a hydroxy group, an alkoxycarbonyl group having 1 to 8 carbon atoms in the alkoxy moiety, an amino group, a nitro group, a cyano group, an alkoxy group having 1 to 8 carbon atoms, a carboxy group, or a phosphate group.
A method of manufacturing eushearilides represented by the formula (I), comprising a step of deprotecting and then cyclizing a compound represented by the formula (I-7):
- wherein R1 represents a hydrogen atom or an optionally substituted hydrocarbon group, wherein the hydrocarbon group is an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkynyl group having 2 to 8 carbon atoms, or an aryl group having 6 to 18 carbon atoms, and wherein the substituent is a hydroxy group, an alkoxycarbonyl group having 1 to 8 carbon atoms in the alkoxy moiety, an amino group, a nitro group, a cyano group, an alkoxy group having 1 to 8 carbon atoms, a carboxy group, or a phosphate group, and P2 represents a protecting group, and R5 represents a hydrocarbon group, wherein the hydrocarbon group is an alkyl group having 1 to 8 carbon atoms an alkenyl group having 2 to 8 carbon atoms, an alkynyl group having 2 to 8 carbon atoms, or an aryl group having 6 to 18 carbon atoms,
- to obtain the eushearilides represented by the formula (I):
- wherein R1 is as defined above, and R2, R3, and R4 independently represent a hydrogen atom or an optionally substituted hydrocarbon group, wherein the hydrocarbon group is an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkynyl group having 2 to 8 carbon atoms, or an aryl group having 6 to 18 carbon atoms, and wherein the substituent is a hydroxy group, an alkoxycarbonyl group having 1 to 8 carbon atoms in the alkoxy moiety, an amino group, a nitro group, a cyano group, an alkoxy group having 1 to 8 carbon atoms, a carboxy group, or a phosphate group.
Dependencies are inferred from the claim text.