Monoterpene Thiols: Synthesis and Modifications for Obtaining Biologically Active Substances

Abstract

Monoterpene thiols are one of the classes of natural flavors that impart the smell of citrus fruits, grape must and wine, black currants, and guava and are used as flavoring agents in the food and perfume industries. Synthetic monoterpene thiols have found an application in asymmetric synthesis as chiral auxiliaries, derivatizing agents, and ligands for metal complex catalysis and organocatalysts. Since monoterpenes and monoterpenoids are a renewable source, there are emerging trends to use monoterpene thiols as monomers for producing new types of green polymers. Monoterpene thioderivatives are also known to possess antioxidant, anticoagulant, antifungal, and antibacterial activity. The current review covers methods for the synthesis of acyclic, mono-, and bicyclic monoterpene thiols, as well as some investigations related to their usage for the preparation of the compounds with antimicrobial properties.

Keywords: antimicrobial activity; asymmetric synthesis; disulfides; monoterpenoids; sulfenimines; sulfinamides; thiols; thiosulfonates.

Scheme 1

The addition of H₂S to limonene 1 catalyzed by AlCl₃.

Scheme 2

The addition of H₂S to α-pinene 8.

Scheme 3

The addition of H₂S to 3-carene 14 catalyzed by AlCl₃.

Scheme 4

Synthesis of camphane thiol 23.

Scheme 5

Synthesis of thiols from sabinene 24.

Scheme 6

Synthesis of allylic terpene thiols 38–42.

Scheme 7

Synthesis of pinane hydroxythiols based on myrtenal 44.

Scheme 8

Synthesis of pinane hydroxythiols based on verbenone 53.

Scheme 9

Synthesis of pinane hydroxythiols based on β-pinene 30.

Scheme 10

Synthesis of β-ketothiol from pinocarvone 61.

Scheme 11

Synthesis of β-ketothiol based on 2-norpinanone 66.

Scheme 12

Synthesis of β-hydroxythiol based on pulegone 73.

Scheme 13

Synthesis of monoterpene hydroxythiols based on 3-carene 14.

Scheme 14

Synthesis of neomenthanethiol 83 and isobornanethiol 13.

Scheme 15

Synthesis of (1S,2S,3R,5R)-3-pinanethiol 93.

Scheme 16

Synthesis of thiogeraniol 100.

Scheme 17

Synthesis of thionerol 103.

Scheme 18

Synthesis of 10-hydroxyisopinocampheylthiol 57 from α- and β-pinene.

Scheme 19

Synthesis of bornane α-hydroxythiol 111 from camphor 112.

Scheme 20

Synthesis of monoterpene hydroxythiols 116 and 120 based on 3-carene 14.

Scheme 21

Sulfenylation of carane thiiranes 121 and 122.

Scheme 22

Scheme for the synthesis of racemic 1-p-menthene-8-thiol 4 and 1-p-menthene-4-thiol 5.

Scheme 23

Synthesis and reduction of para-menthane thiiranes 139 and 140.

Scheme 24

Reductive cleavage of menthone dithiolane 145 and camphor dithiolane 147.

Scheme 25

Synthesis of 10-thioisoborneol 150, 10-thioborneol 151, and 10-thiocamphor 153.

Scheme 26

Reduction of monoterpene sultones 154 and 155.

Scheme 27

Synthesis of sulfenimines, sulfinamides, sulfinimines, and N-substituted sulfinamides based on 4-caranethiol 91.

Scheme 28

Synthesis of sulfenimines based on pinane hydroxythiols.

Scheme 29

Synthesis of asymmetric monoterpenyl hetaryl disulfides (169–172)a–d.

Scheme 30

Synthesis of hydroxypinane thiosulfonates 173 and 174.

Scheme 31

Synthesis thio-monoterpene carboxylic acids (177–178)a–c.

Scheme 32

Synthesis of chiral diols 186a–g using hydroxythiol 43 as a chiral auxiliary.

Scheme 33

Synthesis of chiral 1-phenylethanol 188 using hydroxythiols 111, 151, and 150 as chiral organocatalysts.

Scheme 34

Enantioselective formation of δ-lactone 190 via the treatment of 189 with SmI₂ and chiral thiols 83, 93, 111, and 150.