Thiostreptonhe mea paʻakikī maoli nō ia i hoʻohana ʻia ma ke ʻano he topicallāʻau lāʻau lāʻau lapaʻaua loaʻa pū kekahi hana antimalarial a me ka anticancer maikaʻi.I kēia manawa, ua hoʻohuihui ʻia kemika.
ʻO Thiostrepton, ka mea i hoʻokaʻawale mua ʻia mai ka bacteria i ka makahiki 1955, he hana lāʻau antibiotic ʻokoʻa ia: kaohi ia i ka biosynthesis protein ma ka hoʻopaʻa ʻana i ka ribosomal RNA a me kāna mau protein pili.Ua ʻike ʻo Dorothy Crowfoot Hodgkin, he mea kākau kiʻi kiʻi kiʻi Pelekane a me ka lanakila Nobel Prize i ka makahiki 1964, i ka hale i ka makahiki 1970.
Aia i loko o Thiostrepton he 10 apo, 11 peptide paʻa, unsaturation nui, a me 17 stereocenters.ʻOi aku ka paʻakikī ʻo ka ʻoiaʻiʻo he maʻalahi loa ia i nā waikawa a me nā kumu.ʻO ia ka pūhui makua a me ka lālā paʻakikī o ka ʻohana antibiotic thiopeptide.
I kēia manawa ua hāʻule kēia pūhui i ke kamaʻilio ʻoluʻolu synthetic a ke kumu kemika KS Nicolaou a me kāna mau hoa hana mai ka Scripps Research Institute a me ke Kulanui o Kaleponi ma San Diego [Angew.Kemi.ka honua.Lunahooponopono, 43, 5087 a me 5092 (2004)].
Ua ʻōlelo ʻo Christopher J. Moody, Senior Research Fellow ma ke Keʻena ʻOihana Kimia ma ke Kulanui o Exeter, UK: "He hana hōʻailona hōʻailona kēia a he mea hoʻokō kupaianaha na ka hui Nicolaou."ʻO ka doxorubicin D.
Ki i ka hale oTHIOSTREPTONʻO ke apo dehydropiperidine, e kākoʻo ana i ka huelo didehydroalanine a me ʻelua macrocycles - he apo 26-membered thiazoline-containing a me ka 27-membered quinalcolic acid system.Ua hana ʻo Nicolaou a me nā hoa hana i ke apo dehydropiperidine kī mai nā mea hoʻomaka maʻalahi me ka hoʻohana ʻana i ka biomimetic iso-Diels-Alder dimerization reaction.Ua kōkua kēia hana koʻikoʻi e hōʻoia i ka manaʻo o ka makahiki 1978 e hoʻohana ka bacteria i kēia pane e biosynthesize i nā antibiotics thiopeptide.
Ua hoʻokomo ʻo Nicolaou a me nā hoa hana i ka dehydropiperidine i loko o kahi macrocycle me ka thiazoline.Ua hoʻohui lākou i kēia macrocycle me kahi hale i loaʻa ka quinalcolic acid a me kahi didehydroalanine tail precursor.A laila hoʻomaʻemaʻe lākou i ka huahana e loaʻathiostrepton.
Ua ʻōlelo ka poʻe loiloi o nā pepa ʻelua o ka hui ʻo ka synthesis "he mea hana nui e hōʻike ana i nā ʻenehana hou a wehe i nā ʻike hou no ka noiʻi koʻikoʻi i ke ʻano, ka hana, a me ke ʻano o ka hana."
Ka manawa hoʻouna: ʻOkakopa-31-2023