ʻO Thiostreptonhe huahana bacteria kūlohelohe paʻakikī loa ia i hoʻohana ʻia ma ke ʻano he topicallāʻau antibiotic holoholonaa he hana antimalarial a me anticancer maikaʻi hoʻi. I kēia manawa, ua hoʻohuihui piha ʻia me nā kemika.
ʻO Thiostrepton, i hoʻokaʻawale mua ʻia mai ka bacteria i ka makahiki 1955, he hana antibiotic ʻē aʻe kona: kāohi ia i ka biosynthesis protein ma o ka hoʻopaʻa ʻana i ka ribosomal RNA a me kāna mau protein pili. Ua ʻike ʻo Dorothy Crowfoot Hodgkin, he mea kālai kiʻi kristal Pelekane a me ka mea lanakila Nobel Prize 1964, i ke ʻano i ka makahiki 1970.
Aia i loko o Thiostrepton he 10 mau apo, 11 mau pilina peptide, ka unsaturation nui, a me 17 mau stereocenters. ʻOi aku ka paʻakikī o ka ʻoiaʻiʻo he mea maʻalahi loa ia i nā waikawa a me nā kumu. ʻO ia ka hui makua a me ka lālā paʻakikī loa o ka ʻohana antibiotic thiopeptide.
I kēia manawa, ua hāʻule kēia hui i ka ʻōlelo ʻono synthetic a ke polopeka kemika ʻo KS Nicolaou a me kāna mau hoa hana mai ka Scripps Research Institute a me ke Kulanui o Kaleponi ma San Diego [Angew. Chem. internationality. Editors, 43, 5087 a me 5092 (2004)].
Ua ʻōlelo ʻo Christopher J. Moody, Luna Noiʻi Kiʻekiʻe ma ke Keʻena Kemika ma ke Kulanui o Exeter, UK: "He hana hoʻohui koʻikoʻi kēia a he hoʻokō kupaianaha na ka hui Nicolaou." doxorubicin D.
Kī i ka hoʻonohonoho ʻana oʻO THIOSTREPTONʻo ia ke apo dehydropiperidine, e kākoʻo ana i ka huelo didehydroalanine a me ʻelua macrocycles - he apo thiazoline 26-membered a me kahi ʻōnaehana quinalcolic acid 27-membered. Ua hana ʻo Nicolaou a me nā hoa hana i ke apo dehydropiperidine koʻikoʻi mai nā mea hoʻomaka maʻalahi me ka hoʻohana ʻana i kahi hopena dimerization biomimetic iso-Diels-Alder. Ua kōkua kēia hana koʻikoʻi i ka hōʻoia ʻana i ka manaʻo o 1978 e hoʻohana nā bacteria i kēia hopena e biosynthesize i nā antibiotics thiopeptide.
Ua hoʻokomo ʻo Nicolaou a me nā hoa hana i ka dehydropiperidine i loko o kahi macrocycle i loaʻa i ka thiazoline. Ua hoʻohui lākou i kēia macrocycle me kahi ʻano i loaʻa ka waikawa quinalcolic a me kahi precursor huelo didehydroalanine. A laila ua hoʻomaʻemaʻe lākou i ka huahana e loaʻa aitiostrepton.
Ua ʻōlelo nā mea loiloi o nā pepa ʻelua o ka hui ʻo ka synthesis "he hana noʻeau e hōʻike ana i nā ʻenehana hou loa a wehe i nā ʻike hou no ka noiʻi koʻikoʻi i ka hoʻonohonoho ʻana, ka hana, a me ke ʻano o ka hana."
Ka manawa hoʻouna: ʻOkakopa-31-2023