Raman tag

Patent metadata

Field	Value
Publication number	US-10131687-B2
Application number	US-201715634567-A
Country	US
Kind code	B2
Filing date	Jun 27, 2017
Priority date	Sep 10, 2014
Publication date	Nov 20, 2018
Grant date	Nov 20, 2018

Abstract

A method of forming a probe, wherein the method includes converting cholenic acid into a compound with a terminal alkyne group, wherein the converting the cholenic acid comprises using a sequence, wherein the sequence comprises synthesizing a THP-protection group, LiAlH4 reduction, Dess-Martin oxidation, and Seyferth-Gilbert-Bestmann homologation. The method additionally includes forming A-Chol by removing the THP-protection. Further, the method includes forming PhA-Chol from the compound with the terminal alkyne group via a palladiumcatalyzed Sonogashira reaction. Additionally, the method includes forming PhDY-Chol from the compound with the terminal alkyne group via a coppercatalyzed Cadiot-Chodkiewicz reaction.

First claim

What is claimed is:

1. A method of forming a probe, the method comprising:
converting cholenic acid into a compound with a terminal alkyne group, wherein the converting the cholenic acid comprises using a sequence, wherein the sequence comprises synthesizing a THP-protection group, LiAlH 4 reduction, Dess-Martin oxidation, and Seyferth-Gilbert-Bestmann homologation;
forming alkyne cholesterol (A-Chol) by removing the THP-protection;
forming phenyl-alkyne cholesterol (PhA-Chol) from the compound with the terminal alkyne group via a palladiumcatalyzed Sonogashira reaction; and
forming phenyl-diyne cholesterol (PhDY-Chol) from the compound with the terminal alkyne group via a coppercatalyzed Cadiot-Chodkiewicz reaction.

2. The method of claim 1 , further comprising removing the THP-protection group via an acid.

3. The method of claim 1 , wherein the converting the cholenic acid into the compound with the terminal alkyne group comprises:
adding 3,4-dihydro-2H-pyran (DHP) and p-toluenesulfonic acid monohydrate (p-TsOH) to a mixture of the cholenic acid and THF; and
extracting a first residue, wherein the residue comprises:

4. The method of claim 3 further comprising:
adding the first residue to a suspension of LiAlH 4 in dry THF;
extracting a second residue, wherein the second residue comprises:

5. The method of claim 4 further comprising:
adding Dess-Martin Periodinane to a suspension of the second residue and NaHCO 3 ; and
extracting a third residue, wherein the third residue comprises:

6. The method of claim 5 further comprising:
adding dimethyl-1-diazo-2-oxopropylphosphonate to a solution of the third residue and K 2 CO 3 ;
extracting a fourth residue, wherein the fourth residue comprises:

7. The method of claim 4 further comprising:
adding methanesulfonyl chloride to a solution of the second residue and trimethylamine in CH 2 Cl 2 ;
extracting a fifth residue, wherein the fifth residue comprises:

8. The method of claim 7 further comprising:
adding potassium cyanide to a solution, wherein the solution comprises the fifth residue and DMSO;
extracting a sixth residue, wherein the sixth residue comprises:

9. The method of claim 8 further comprising:
dissolving the sixth residue and p-toluenesulfonic acid monohydrate in THF and methanol;
extracting a seventh residue, wherein the seventh residue comprises:

10. The method of claim 6 further comprising:
dissolving the fourth residue and p-toluenesulfonic acid monohydrate in THF and methanol;
extracting an eighth residue, wherein the eighth residue comprises:

11. The method of claim 6 further comprising:
mixing the fourth residue with CuI, iodobenzene, and trimethylamine;
extracting a ninth residue, wherein the ninth residue comprises:

12. The method of claim 11 further comprising:
dissolving the ninth residue and p-toluenesulfonic acid monohydrate in THF and methanol;
extracting a tenth residue, wherein the tenth residue comprises:

13. The method of claim 6 further comprising:
mixing the fourth residue, CuI, P(o-Tol) 3 , K 2 CO 3 , compound A, and anhydrous EtOH, wherein the compound A comprises:

extracting an eleventh residue, wherein the eleventh residue comprises:

14. The method of claim 13 further comprising:
dissolving the eleventh residue and p-toluenesulfonic acid monohydrate in THF and methanol;
extracting a twelfth residue, wherein the twelfth residue comprises:

15. The method of claim 6 further comprising:
mixing the fourth residue, PdCl 2 (PPh 3 ) 2 , CuI, compound B, and THF, wherein the compound B comprises:

extracting a thirteenth residue, wherein the thirteenth residue comprises:

16. The method of claim 15 further comprising:
dissolving the thirteenth residue and p-toluenesulfonic acid monohydrate in THF and methanol;
extracting a fourteenth residue, wherein the fourteenth residue comprises:

Assignees

• Purdue Research Foundation

Inventors

• Dai Mingji

Classifications

• C07J41/0094

  containing nitrile radicals, including thiocyanide radicals · CPC title

• G01N33/52

  Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper {and including single- and multilayer analytical elements (immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72)} · CPC title

• C07J9/00 Primary

  Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane · CPC title

• C07J17/00

  Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton (cardanolide, bufanolide C07J19/00) · CPC title

• C07J9/005

  containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton · CPC title