Akuammicine

The alkaloids are a large group of natural products which are classified according to the part-structure which members of a particular group contain. Akuammicine is a monoterpene indole alkaloid of the Vinca sub-group which shares a common biosynthesis with other members, namely that they are derived from strictosidine.{{cite book|author = Dewick, Paul M |title = Medicinal Natural Products. A Biosynthetic Approach. Second Edition|pages=350–359|url = https://books.google.com/books?id=A4zptjOJfKQC&pg=PP1|year = 2002|publisher = Wiley|isbn = 0-471-49640-5}}{{cite journal |doi=10.1039/NP9840100021 |title=Recent progress in the chemistry of indole alkaloids and mould metabolites |year=1984 |last1=Saxton |first1=J. E. |journal=Natural Product Reports |volume=1 |page=21 }} It was first isolated in 1927 and had been investigated by Sir Robert Robinson and others before its structure was correctly deduced.{{cite journal |doi=10.1039/JR9600000792 |doi-access= |title=161. Akuamma alkaloids. Part I. Akuammicine |year=1960 |last1=Smith |first1=G. F. |last2=Wróbel |first2=J. T. |journal=J. Chem. Soc. |pages=792–795 }}{{cite journal |doi=10.1007/BF00580558 |title=NMR investigation of alkaloids. IV. ¹³C NMR spectra and structures of norfluorocurarine, akuammicine, vincanidine, and vinervinine |year=1983 |last1=Yagudaev |first1=M. R. |journal=Chemistry of Natural Compounds |volume=19 |issue=2 |pages=199–201 |s2cid=28255077 }} This was confirmed by X-ray crystallography in 2017.{{cite journal |doi=10.1107/S2056989017014529 |title=Crystal structure of akuammicine, an indole alkaloid from Catharanthus roseus |year=2017 |last1=Yahyazadeh |first1=Mahdi |last2=Jerz |first2=Gerold |last3=Selmar |first3=Dirk |last4=Winterhalter |first4=Peter |last5=Jones |first5=Peter G. |journal=Acta Crystallographica Section E |volume=73 |issue=11 |pages=1658–1661 |pmid=29152344 |pmc=5683484 |bibcode=2017AcCrE..73.1658Y }}

File:Picralima Nitida - 05.jpg

Akuammicine is found in plants of the Apocynaceae family and was first isolated from Picralima nitida. It has also been reported in Catharanthus roseus.{{cite journal |doi=10.1016/0031-9422(80)83216-X |title=Formation of catharanthine, akuammicine and vindoline in Catharanthus roseus suspension cells |year=1980 |last1=Scott |first1=A.Ian |last2=Mizukami |first2=Hajime |last3=Hirata |first3=Toshifumi |last4=Lee |first4=Siu-Leung |journal=Phytochemistry |volume=19 |issue=3 |pages=488–489 |bibcode=1980PChem..19..488S }}

{{Main|Indole alkaloid#Biosynthesis}}

As with other indole alkaloids, the biosynthesis of akuammicine starts from the amino acid tryptophan. This is converted into strictosidine before further elaboration.

File:Strychnine.svg

Akuammicine has been a target for total synthesis,{{cite journal |doi=10.1038/nature10232 |title=Collective synthesis of natural products by means of organocascade catalysis |year=2011 |last1=Jones |first1=Spencer B. |last2=Simmons |first2=Bryon |last3=Mastracchio |first3=Anthony |last4=MacMillan |first4=David W. C. |journal=Nature |volume=475 |issue=7355 |pages=183–188 |pmid=21753848 |pmc=3439143 }} partly because of its relationship to the well-known alkaloid strychnine which has often attracted chemists in academia.{{cite journal |doi=10.1021/ja010935v |title=Biogenetically Inspired Approach to the Strychnos Alkaloids. Concise Syntheses of (±)-Akuammicine and (±)-Strychnine |year=2001 |last1=Ito |first1=Masayuki |last2=Clark |first2=Cameron W. |last3=Mortimore |first3=Michael |last4=Goh |first4=Jane Betty |last5=Martin |first5=Stephen F. |journal=Journal of the American Chemical Society |volume=123 |issue=33 |pages=8003–8010 |pmid=11506556 }}{{cite journal |doi=10.1021/jo100516g |title=Concise Total Syntheses of (±)-Strychnine and (±)-Akuammicine |year=2010 |last1=Sirasani |first1=Gopal |last2=Paul |first2=Tapas |last3=Dougherty |first3=William |last4=Kassel |first4=Scott |last5=Andrade |first5=Rodrigo B. |journal=The Journal of Organic Chemistry |volume=75 |issue=10 |pages=3529–3532 |pmid=20408591 }}{{cite book |doi=10.1016/B978-0-08-099362-1.00001-1 |title=Total Synthesis of Strychnos Alkaloids Akuammicine, Strychnine, and Leuconicines a and B |series=Strategies and Tactics in Organic Synthesis |year=2013 |last1=Sirasani |first1=Gopal |last2=Andrade |first2=Rodrigo B. |volume=9 |pages=1–44 |isbn=978-0-08-099362-1 }}{{cite journal |doi=10.1002/anie.201611734 |title=Reaction of Donor-Acceptor Cyclobutanes with Indoles: A General Protocol for the Formal Total Synthesis of (±)-Strychnine and the Total Synthesis of (±)-Akuammicine |year=2017 |last1=Feng |first1=Liang-Wen |last2=Ren |first2=Hai |last3=Xiong |first3=Hu |last4=Wang |first4=Pan |last5=Wang |first5=Lijia |last6=Tang |first6=Yong |journal=Angewandte Chemie International Edition |volume=56 |issue=11 |pages=3055–3058 |pmid=28170147 }}

Plant metabolites have long been studied for their biological activity and alkaloids in particular are major subjects for ethnobotanical research.{{cite journal |doi=10.1039/C5RA01912E |title=The chemistry and bioactivity of Southern African flora I: A bioactivity versus ethnobotanical survey of alkaloid and terpenoid classes |year=2015 |last1=Babiaka |first1=Smith B. |last2=Ntie-Kang |first2=Fidele |last3=Lifongo |first3=Lydia L. |last4=Ndingkokhar |first4=Bakoh |last5=Mbah |first5=James A. |last6=Yong |first6=Joseph N. |journal=RSC Advances |volume=5 |issue=54 |pages=43242–43267 |bibcode=2015RSCAd...543242B }} Akuammicine is reported to have effects on glucose uptake and be a κ- and μ-opioid receptor agonist.{{cite journal |doi=10.1016/s0014-2999(98)00232-5 |title=Opioid activity of alkaloids extracted from Picralima nitida (Fam. Apocynaceae) |year=1998 |last1=Menzies |first1=John R.W |last2=Paterson |first2=Stewart J. |last3=Duwiejua |first3=Mahama |last4=Corbett |first4=Alistair D. |journal=European Journal of Pharmacology |volume=350 |issue=1 |pages=101–108 |pmid=9683021 }}

• Ajmalicine
• Vinervine, the 12-hydroxy derivative

{{Reflist}}

Category:Vinca alkaloids

Category:Alkaloids found in Apocynaceae