Diversity-oriented synthesis of medicinally important 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) derivatives and higher analogs

Abstract

1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid (Tic) is a constrained analog of phenylalanine (Phe). The Tic unit has been identified as a core structural element present in several peptide-based drugs and forms an integral part of various biologically active compounds. This report covers the biological significance of the Tic core and provides a detailed account of various synthetic approaches available for the construction of Tic derivatives. Along with the traditional methods such as the Pictet-Spengler and Bischler-Nepieralski reactions, we cover various recent approaches such as enyne metathesis, [2 + 2 + 2] cycloaddition and the Diels-Alder reaction to generate Tic derivatives. In addition, syntheses of higher analogs of Tic are also discussed.

Chemoenzymatic Approach to (S)‐1,2,3,4‐Tetrahydroisoquinoline Carboxylic Acids Employing D‐Amino Acid Oxidase

“…Compared with chiral 3‐carboxyl substituted THIQs, which could be synthesized from the corresponding chiral amino acids (e. g., L‐phenylalanine), asymmetric synthesis of chiral 1‐carboxyl substituted THIQs are more difficult. Having obtained the Fs DAAO and applied it for the kinetic resolution of carboxyl‐substituted THIQs successfully, we attempted to investigate a novel method for the synthesis of ( S )‐carboxyl substituted THIQs, especially for the 1‐carboxyl substituted THIQs, by combination of Fs DAAO with a chemical reducing agent in one pot.…”

“…Considerable effort has been devoted to the enantioselective preparation of chiral THIQs. Chemical asymmetric synthesis method are important and frequent sources of these compounds . However, the use of hazardous materials, such as toxic organic reagents or transition metal catalysts, remains a challenge for industrial application.…”

Succinct Syntheses of Methopholine, (±)‐Homolaudanosine, and (±)‐Dysoxyline via Metal‐free One‐Pot Double Alkylation on 1‐Methyl‐3,4‐dihydroisoquinolines

“…Through solvent screening processes, DCE and CH 3 CN turned out to be better than other solvents for the formation of double alkylating product 3a (entries [2][3][4][5][6]. As alkylation at the C1-methyl of iminium salt was known to be enabled by converting iminium salt to enamine with the help of bases, 31,32 addition of bases, such as Na 2 CO 3 , DIPEA, Et 3 N, DBU, and NMP, was performed in DCE and CH 3 CN (entries [7][8][9][10][11][12][13][14][15][16].…”

“…[1][2][3][4][5][6] Numerous methodologies have been reported for the syntheses of THIQ analogs. 1,3,6 In particular, THIQs substituted at the C1 and N positions display various biological activities, such as antitumor, 7-10 anti-HIV, [11][12][13] antibacterial, 1,14 and neuroprotective. 15,16 For instance, solifenacin is an approved drug as a selective muscarinic M3 receptor antagonist for the treatment of overactive bladder ( Figure 1).…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…Specific compounds or compound classes represented include: (1) tetrahydropyrans [53]; (2) cyclopentenones [54]; (3) 3,4,5-trisubstituted isoxazolines [55]; (4) carbocyclic nucleosides [56]; (5) lycopodium alkaloids [57,58]; (6) cyclic hydrazines and azo compounds [59]; (7) tropone and tropolone natural products [60]; (8) seven-membered ring natural products [61]; [62]; (9) tetrahydroisoquinoline-3-carboxylic acid derivatives [63]; (10) chalcones and their heterocyclic derivatives [64]; (11) marine-derived cyclic ethers [65]; (12) pericosine and related marinederived carbasugar natural products [66]; (13) carbohydrate derived macrocyclic compounds [67]; (14) neurotrophic natural products [68]; (15) isodon diterpenes [69]; (16) non-isoprenoid polyene natural products [70]; (17) heterophosphacyclanes [71]; (18) chlorosulfolipids [72]; (19) seven-membered ring sulfur heterocycles; (20) organic cage compounds [73]; (21) presilphiperfolanols [74]; (22) pleuromutilin [75]; (23) hyperforin [76]; (24)…”