SYNTHESIS OF ISONITRILE COMPOUNDS (GLU-OiPR-OBZ3 AND GLU-OiPR-OCT3) AS NEW ANTI FOULING AGENTS BASED ON D-GLUCOSAMINE

IRA NOVITA SARI, Prof. Drs. Jumina, Ph.D. ; Tri Joko Raharjo, S.Si., M.Si., Ph.D.

2016 | Tesis | S2 Ilmu Kimia

Dua agen antifouling yaitu Glu-OiPr-Obz3 (isonitril 31) dan Glu-OiPr-Oct3 (isonitril 33) telah disintesis dari D-glukosamin dan diuji aktivitas antifouling-nya. Senyawa isonitril 31 dan 33 dicapai melalui jalur sintesis sederhana (7 tahapan reaksi) yang menghasilkan 5 senyawa intermediet utama dalam prosesnya. Senyawa intermediet tersebut adalah ftalimida 27, ester 28, formamida 29, formamida 30 dan isonitril 31. Reaksi tahap pertama dan kedua (proteksi amin menggunakan ftalil anhidrida dan proteksi alkohol menggunakan asetat anhidrida) menghasilkan intermediet pertama yaitu phthalimide 27 dengan yield sebesar 64%. Kemudian reaksi glikosilasi dilakukan sebagai tahap ketiga menggunakan isopropil alkohol menghasilkan ester 28 dengan yield sebesar 30%. Formamida 29 dihasilkan melalui 2 tahapan reaksi, yaitu deproteksi gugus ftaloil dan gugus asetil menggunakan etilendiamina kemudian reaksi formilasi menggunakan metil format dan metanol. Reaksi asiliasi menggunakan asil klorida menghasilkan dua produk asilasi. Produk asilasi pertama (formamida 30) dihasilkan dengan mereaksikan formamida 29 dan benzoil klorida pada suhu 60°C dengan yield sebesar 46%. Kemudian produk asilasi kedua (formamida 32) dihasilkan dengan mereaksikan formamida 29 dan oktanoil klorida pada suhu kamar dengan yield sebesar 24%. Produk akhir didapatkan melalui reaksi isonitrilasi (tahap ketujuh) dengan yield sebesar 35% untuk isonitril 31 dan yield sebesar 60% untuk isonitril 32. Nilai konfigurasi absolut dari setiap senyawa sudah ditentukan pada setiap langkah sintesis. Hasil uji aktivitas antifouling (EC50) senyawa isonitril 31 dan 33 terhadap larva cypris Amphibalanus amphitrite didapatkan sebesar 0.81 dan 0.79 mikrogram/mL secara berurutan dengan nilai toksisitas yang rendah (LC50 >10 mikrogram/mL).

Two new antifouling agents that are Glu-OiPr-Obz3 (isonitrile 31) and Glu-OiPr-Oct3 (isonitrile 33) have been synthesized from D-glucosamine and their antifouling activites have been examined. The compounds of isonitrile 31 and 33 were achieved by simple synthesis pathway (7 step of reactions) which produced 5 important intermediate compounds in its process. These intermediates were phthalimide 27, ester 28, formamide 29, formamide 30 and isonitrile 31. First and second step of reactions (amine protection using phtalic anhydride and alcohol protection using acetic anhydride) gave first intermediate of phtalimide 27 in 64% yield. Then glycosylation reaction has been conducted as third step of reaction using isopropyl alcohol to provide ester 28 in 30% yield. Formamide 29 was produced by 2 step of reactions, i.e. deprotection of phthaloyl and acetyl groups using ethylene diamine then formylation reaction using methyl formate and methanol. Acylation reaction using acyl chloride as sixth step produced two acylated products. The first acylated product (formamide 30) was produced by reacting formamide 29 and benzoyl chloride at temperature of 60°C in 46% yield. Then second acylated product (formamide 32) was produced by reacting formamide 29 and octanoyl chloride at room temperature in 24% yield. Final products were achieved via isonitrilation reaction (seventh step) in 35% yield of isonitrile 31 and 60% yield of isonitrile 32. Absolute configurations of the product were established through total synthesis. Antifouling activity (EC50) results of isonitrile 31 and 33 against cypris larvae of Amphibalanus amphitrite were 0.81 and 0.79 microgram/mL respectively without significant toxicity (LC50 >10 microgram/mL).

Kata Kunci : Antifouling agents, D-glucosamine, Isonitrile 31 and 33