US 2026/0201433 A1Published application

Chemoenzymatic synthesis of polyketides

AssigneeAspera Biomedicines, Inc.

InventorsCatriona H. M. Jamieson, James J. La Clair, Michael D. Burkart

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Abstract

Provided herein are synthetic methods and intermediates useful in the preparation of polyketides. The polyketides include 12-membered ring macrolides. These synthetic methods and intermediates provide scalable access to polyketides, which include polyketides having potent bioactive splice modulator activity and potential for therapeutic applications including treating diverse types of cancers.

Claims20

Dependent claims

A compound, selected from:

or a salt thereof,
wherein
R1 is C1-6 alkyl, and
R2 is an organotin moiety including a Tin (Sn) atom covalently linked with the carbon to which R2 is attached.

1 more element

A method of preparing a synthesized compound, comprising at least one of the following steps:

Step 1) preparing a mixture comprising at least one solvent, 10-camphorsulfonic acid, and Compound 1
to form Compound 2
Step 2) preparing a mixture comprising at least one solvent, an acid, 1-(dimethoxymethyl)-4-methoxy-benzene, and Compound 2
to form Compound 3
Step 4) preparing a mixture comprising at least one solvent, lithium diisopropylamide, and Compound 4
to form Compound 5
Step 5) preparing a mixture comprising at least one solvent, 2-iodoxybenzoic acid, and Compound 5
to form Compound 6
or
preparing a mixture comprising at least one solvent, N,N′-dicyclohexylcarbodiimide, pyridine·trifluoroacetic acid, and Compound 5
to form Compound 6
Step 6) preparing a mixture comprising at least one solvent, an enzyme having aldo-keto reductase activity, a reducing cofactor selected from NADPH or NADH, an auxiliary enzyme and substrate for cofactor regeneration, and Compound 6
to form Compound 7
Step 7) preparing a mixture comprising at least one solvent, tert-butyldimethylsilyl chloride, an imidazole, tert-butyldimethylsilyl trifluoromethanesulfonate, a base, and Compound 7
to form Compound 8
Step 8) preparing a mixture comprising at least one solvent, a base, and Compound 8
to form Compound 9
Step 15b) preparing a mixture comprising at least one solvent, a silanyl chloride, Compound 19, and Compound 19
to form a reaction product, and chromatographically purifying the reaction product over silica gel to form Compound 19 or Compound 19R having an EE of at least 99%;
Step 15c) preparing a mixture comprising at least one solvent, Compound 19, Compound 19R, and an oxidizing agent
to form Compound 19O;
Step 15d) preparing a mixture comprising at least one solvent, an enzyme having aldo-keto reductase activity, a reducing cofactor selected from NADPH or NADH, an auxiliary enzyme and substrate for cofactor regeneration, and Compound 190
to form Compound 19
Step 16) preparing a mixture comprising at least one solvent, tributyltin hydride, and Compound 19 or Compound 19R
to form Compound 20 or Compound 20R (or instead using trimethyltin hydride to form the corresponding vinyl trimethyl tin compound)
Step 17) preparing a mixture comprising Compound 20 or Compound 20R, and Compound 14
to form Compound A or Compound B
Step 4a) preparing a mixture comprising at least one solvent, Compound 4
and Compound 21
to form Compound 22
Step 5a) preparing a mixture comprising at least one solvent, and Compound 22
and oxidizing Compound 22 to form Compound 23
Step 6a) preparing a mixture comprising at least one solvent, and Compound 23
and reducing Compound 23 to form Compound 24
Step 7a) preparing a mixture comprising at least one solvent, tert-butyldimethylsilyl chloride, a base, and Compound 24
to form Compound 11
Step 3b) preparing a mixture comprising at least one solvent, and Compound 3
and oxidizing Compound 3 to form Compound 25
Step 4b) preparing a mixture comprising at least one solvent, a peptide coupling reagent, and Compound 25
to form Compound 26
or
Step 5b) preparing a mixture comprising at least one solvent, a dimethylhydroxylamine, a base, and Compound 26
to form Compound 6

40 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/134,662Filed 1 Dec 2023
Priority: 1 Dec 2022
Published: 16 Jul 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification21 codes

C12P 17/02
Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms: oxygen as only ring hetero atoms
A61K 31/365
Having oxygen as the only ring hetero atom, e.g. fungichromin: lactones
C07C 33/035
With only one double bond: alkenediols
C07D 303/02
Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom: compounds containing oxirane rings

Family

Application63/429,356Us provisional application · filed 1 Dec 2022
Application63/432,011Us provisional application · filed 12 Dec 2022
US 2026/0201433 A1This patent

From the US filing history. Foreign family members aren’t listed.

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