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US 10,119,155 B2Granted
Compositions and methods for making (S)-norcoclaurine and (S)-norlaudanosoline, and synthesis intermediates thereof
AssigneeEpimeron Inc.
InventorPeter James Facchini
Life of this patent
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Abstract
Methods that may be used for the manufacture of the chemical compound (S)-norcoclaurine, (S)-norlaudanosoline, and (S)-norcoclaurine or [S]-norlaudanosoline synthesis intermediates are provided. (S)-Norcoclaurine, (S)-norlaudanosoline, and (S)-norcoclaurine or (S)-norlaudanosoline synthesis intermediates are useful as precursor products in the manufacture of certain medicinal agents.
Claims12
The method of making (S)-norcoclaurine or (S)-norlaudanosoline, comprising:
- (a) providing at least one (S)-norcoclaurine or (S)-norlaudanosoline pathway precursor selected from a first L-tyrosine derivative;
- and
- (b) contacting the (S)-norcoclaurine or (S)-norlaudanosoline pathway precursor with at least one of the enzymes selected from the group of enzymes consisting of (i) monoamine oxidase (MAO);
- and (ii) norcoclaurine synthase (NCS) under reaction conditions permitting the catalysis of the (S)-norcoclaurine or (S)-norlaudanosoline pathway precursor to form (S)-norcoclaurine or (S)-norlaudanosoline;
- and
- wherein the first L-tyrosine derivative has the chemical formula (1):
- wherein R1 represents hydrogen or hydroxyl;
- wherein R2 represents hydrogen;
- and
- wherein R3 represents an amino group —(NH2);
- and
- wherein R3′ represents a hydrogen atom, provided R1 represents hydroxyl;
- or
- wherein R3 and R3′ taken together, form a carbonyl group;
- and wherein monoamine oxidase (MAO) is a polypeptide having the sequence set forth in SEQ.ID. NO. 96;
- and
- and wherein norcoclaurine synthase (NCS) is a polypeptide having a sequence selected from the group of sequences set forth in SEQ.ID NO:
- 13;
- SEQ.ID NO:
- 14;
- SEQ.ID NO:
- 17;
- SEQ.ID NO:
- 28;
- SEQ.ID NO:
- 34;
- and SEQ.ID NO:
- 42;
- or is encoded by SEQ.ID NO:
- 109 or SEQ.ID NO:
- 113.
28 more elements
A method for preparing (S)-norcoclaurine or (S)-norlaudanosoline;
- comprising:
- (a) providing a chimeric nucleic acid sequence comprising as operably linked components:
- (i) one or more nucleic acid sequences encoding one or more of the D polypeptides selected from the group of polypeptides consisting of monoamine oxidase (MAO);
- and NCS norcoclaurine synthase (NCS);
- and
- (ii) one or more nucleic acid sequences capable of controlling expression in a host cell;
- (b) introducing the chimeric nucleic acid sequence into a host cell and growing the host cell to produce the polypeptide selected from the group of polypeptides consisting of monoamine oxidase (MAO);
- and norcoclaurine synthase (NCS) and to produce one or more of (S)-norcoclaurine or (S)-norlaudanosoline;
- (c) recovering (S)-norcoclaurine, or (S)-norlaudanosoline;
- wherein monoamine oxidase (MAO) is a polypeptide having the sequence set forth in SEQ.ID. NO. 96;
- and wherein NCS norcoclaurine synthase (NCS) is a polypeptide having a sequence selected from the group of sequences set forth in SEQ.ID NO:
- 13;
- SEQ.ID NO:
- 14;
- SEQ.ID NO:
- 17;
- SEQ.ID NO:
- 28;
- SEQ.ID NO:
- 34;
- and SEQ.ID NO:
- 42;
- or is encoded by SEQ.ID NO:
- 109 or SEQ.ID NO:
- 113.
22 more elements
A method for preparing an (S)-norcoclaurine or (S)-norlaudanosoline pathway precursor selected from the group consisting of:
- dopamine;
- 4-hydroxyphenylacetaldehyde;
- and 3,4-dihydroxyphenylacetaldehyde;
- and comprising:
- (a) providing a chimeric nucleic acid sequence comprising (i) one or more nucleic acid sequences complementary all or a portion of the mRNA synthesized by the nucleic acid sequence encoding the polypeptides selected from the group of polypeptides consisting of monoamine oxidase (MAO);
- and norcoclaurine synthase (NCS);
- and (ii) one or more elements capable of controlling transcription of the complementary nucleic acid sequence, wherein the chimeric nucleic acid sequence is capable of producing an antisense RNA complementary all or a portion of the mRNA of the nucleic acid sequence encoding the polypeptides selected from the group of polypeptides consisting of MAO;
- and norcoclaurine synthase (NCS);
- (b) introducing the chimeric nucleic acid sequence into a host cell;
- (c) growing the host cell to produce the antisense RNA and inhibit synthesis of the polypeptide selected from the group of polypeptides consisting of monoamine oxidase (MAO);
- and norcoclaurine synthase (NCS) and to produce one or more of an norcoclaurine or (S)-norlaudanosoline pathway precursors selected from the group consisting of:
- dopamine;
- and 4HPAA and 3,4 HPAA;
- and
- (d) recovering a (S)-norcoclaurine pathway precursor or (S)-norlaudanosoline pathway precursor selected from the group consisting of dopamine;
- 4-hydroxyphenylacetaldehyde;
- and 3,4-dihydroxyphenylacetaldehyde;
- wherein monoamine oxidase (MAO) is a polypeptide having the sequence set forth in SEQ.ID. NO. 96;
- and wherein norcoclaurine synthase (NCS) is a polypeptide having a sequence selected from the group of sequences set forth in SEQ.ID NO:
- 13;
- SEQ.ID NO:
- 14;
- SEQ.ID NO:
- 17;
- SEQ.ID NO:
- 28;
- SEQ.ID NO:
- 34;
- and SEQ.ID NO:
- 42;
- or is encoded by SEQ.ID NO:
- 109 or SEQ.ID NO:
- 113.
30 more elements
Dependencies are inferred from the claim text.