Processes and compounds for preparing spiroligomers
AssigneesTemple University of the Commonwealth System of Higher Education, ThirdLaw Molecular Inc.
InventorsChristian Schafmeister, Justin Northrup
Life of this patent
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Abstract
The present invention provides novel intermediates and other compounds prepared using compounds of Formula I. These novel compounds include spiroligomers that have particular significance in the peptide industry. The processes described herein provide products that are produced in high yields in high purities and, thus, are highly efficient.
Claims70
A process comprising contacting a compound of Formula I with R1X, R1C(O)H, or R1C(O)R2:
- wherein:
- R1 is selected from the group consisting of an amino acid, β-amino acid, sugar, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted aryl, and any combination thereof;
- R2 is absent or selected from the group consisting of H, amino acid, β-amino acid, sugar, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted aryl, and any combination thereof;
- or R1 and R2 are linked to form a C3-8 cycloalkyl;
- X is a leaving group;
- R4 is a protecting group;
- x is an integer 1 or 2;
- and
- z is an integer 1 or 2;
- with the proviso that both x and z are not 2;
- in the presence of a reducing agent;
- for a time and under conditions effective to produce a compound of Formula II:
- wherein:
- y is an integer 0 or 1;
- with the proviso that when the compound of Formula I is reacted with R1X, y is an integer 0 and R2 is absent.
A process for preparing a compound of Formula I:
- wherein R4 is a protecting group;
- x is an integer 1 or 2;
- and
- z is an integer 1 or 2;
- with the proviso that both x and z are not 2;
- comprising contacting a compound of Formula III:
- wherein M is a transition metal with a +2 oxidation state;
- with a chelator for a time and under conditions effective to produce the compound of Formula I.
A process for preparing a compound of Formula III:
- wherein R4 is a protecting group;
- x is an integer 1 or 2;
- and
- z is an integer 1 or 2;
- with the proviso that both x and z are not 2;
- comprising contacting a compound of Formula IV:
- with 9-fluorenylmethoxycarbonyl chloride;
- for a time and under conditions effective to produce the compound of Formula III.
A process for preparing a compound of Formula IV:
- comprising contacting a compound of Formula V:
- with a metal (II) source;
- for a time and under conditions effective to produce the compound of Formula IV.
A process for preparing a compound of Formula VII:
- comprising contacting a compound of Formula II:
- with a compound of Formula VI:
- wherein AA is an optionally substituted amino acid;
- and
- R5 is a resin;
- with an activating agent and a base to provide an intermediate;
- and
- contacting the intermediate with a deprotectant for a time and under conditions effective to produce the compound of Formula VII.
A process for preparing a compound of Formula XV:
- wherein R1 is selected from the group consisting of optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted aryl, and any combination thereof;
- R2 is absent or selected from the group consisting of H, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted aryl, and any combination thereof;
- or R1 and R2 are linked to form a C3-8 cycloalkyl;
- R4 is a protecting group;
- x is an integer 1 or 2;
- and
- z is an integer 1 or 2, with the proviso that both x and z are not 2;
- w is an integer 1 to 20;
- and
- y is an integer 0 or 1;
- comprising:
- a) contacting a compound of Formula II with a compound of Formula VI:
- wherein AA is an optionally substituted amino acid;
- and
- R5 is a resin;
- and
- with an activating agent and a base to provide an intermediate;
- b) contacting the intermediate with a deprotectant for a time and under conditions effective to produce the compound of Formula VII:
- and
- c) contacting the compound of Formula VII with the compound of Formula II (w-1) times.
A compound of Formula II:
- wherein y is an integer 0 or 1;
- R1 is selected from the group consisting of optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted aryl, and any combination thereof;
- R2 is absent or selected from the group consisting of H, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted aryl, and any combination thereof;
- or R1 and R2 are linked to form a C3-8 cycloalkyl.
- R4 is a protecting group;
- or a pharmaceutically acceptable salt thereof.
A compound having the structure of:
A compound having the structure of:
A compound having the structure of:
Dependencies are inferred from the claim text.