Ambroxan Sauvage is an artificial spice with an unique fragrance of all-natural ambergris. All-natural ambergris (Ambergris) is a valuable pet flavor. It is a sort of stone in the tummy of sperm whale. It is vomited or secreted on the sea surface by the whale, as well as it emits an unique fragrance airborne for a very long time. The synthesis of Ambroxan Sauvage utilizes perillyl alcohol as basic material, as well as is oxidized by KMnO4 in two actions (Switzerland utilizes ozone oxidation, Russia makes use of sodium chromate oxidation). That is (1) alkaline oxidation; (2) weak acid oxidation. The oxide is gotten, and then the oxide is soaped, dehydrated and lactonized to obtain ambroxolide. The lactone is minimized to ambroxol utilizing lithium aluminum hydride in ether (or borane in tetrahydrofuran).
Technique 1: Usage sclareol as raw material to execute two-step oxidation, namely alkaline oxidation and weak acid oxidation. The oxidant can be potassium permanganate, ozone or salt (or potassium) dichromate sulfuric acid option, and then oxidize Saponification, dehydration, and also lactonization of the material are utilized to obtain ambroxolide. The lactone is then minimized to ambroxol using lithium aluminum hydride in ether (or borane in tetrahydrofuran). Ambroxan can be prepared by utilizing D-camphor-β-sulfonic acid as a cyclizing agent, decyclizing the diol, and then dehydrating it under the activity of light weight aluminum oxide. In addition to getting Ambroxan Sauvage by this technique, bicyclic homofarnesol, an isomer of ambroxan, can also be acquired, that is, lipid-6-en-12-ol (anemic crystal, melting point 20 ° C, There is also ambergris taste).
Technique 2: Artificial course utilizing diol 2 as an intermediate
Ambroxan Sauvage was synthesized synthetically for the very first time from (-)- sclareol 3 in sclare remove, with a total yield of 52%. Sclareol 3 is oxidized with chromium trioxide and broken down to lactone 4, and lactone 4 is reduced by tetrahydroaluminum lithium to acquire diol 2; diol substance 2 is triggered by p-toluenesulfonyl chloride, and after that performed under the action of alkali salt hydride. Intramolecular cyclization gave Ambergris 1. The drawback of this path is that it needs to make use of chromium trioxide as an oxidant, which will create a large amount of seriously polluted chromium-containing wastewater, and also at the same time, it requires to utilize lithium tetrahydroaluminum as well as sodium hydride with high threat.
Opportunity to synthesize Ambroxan Sauvage by stereoselective cyclization using nerolidol 5 as beginning product. Beginning with nerolidol 5, with bromination, nitrification and also hydrolysis, (E, E)- homofacamic acid 8 and also one more isomer were obtained in a ratio of 8:2. Acid 8 was cleansed by column chromatography by creating an ethyl ester, as well as the ester of 8 was hydrolyzed under basic conditions to generate the acid in 98% pureness. Acid 8 was reacted with boron trifluoride ether as Lewis acid in dichloromethane at -20 ° C for 60 mins to acquire cyclized product 4 with a yield of 38%. After that, substance 4 is decreased with lithium aluminum tetrahydrogen to get diol 2, as well as diol 2 is heated in the existence of driver p-toluenesulfonic acid making use of pyridine as a solvent, as well as cyclized to obtain ( ±) ambroxan 1, which is obtained The rate is 75%.
Technique 3: Artificial course without intermediate diol 2
Beginning with dihydro β-ionone 35, 4-(2,2,6-trimethyl-1-cyclohexene)-2-methylbutanal 47 was gotten by Darzens reaction, which was after that reacted with malonic acid to get 48, and after that after numerous actions of response, ambroxan 1 is acquired. The item gotten right here is a racemate with a somewhat different fragrance quality from (-)-Ambroxan Sauvage.
