During our attempt to follow the planned synthetic route to the naturally occurring antibiotic (–)-atrop-abyssomicin C, we encountered two shortcomings, which forced us to reconsider our tactics and find new methods to overcome the problems. These methods turned out to be of general applicability, as demonstrated later in total syntheses of two other natural products: (+)-allokainic acid and (-)-gabosine H. The paper provides a brief account of these endeavors.
BisterB., BischoffD., StröbeleM., RiedlingerJ., ReickeA., WolterF., BullA.T., FiedlerH.P., SüssmuthR.D. (2004) Abyssomicin C—A polycyclic antibiotic from a marine Verrucosispora strain as an inhibitor of the p-aminobenzoic acid/tetrahydrofolate biosynthesis pathway. Angewandte Chemie International Edition, 43, 2574–2576.
2.
For a chapter on abyssomicins in the book, see: NicolaouK.C., ChenJ.S.: Classics in Total Synthesis III, Wiley VCH, Veinheim, 2011.
3.
(a) ZapfC.W., HarrisonB.A., DrahlC., SorensenE.J. (2005) A Diels–Alder macrocyclization enables an efficient asymmetric synthesis of the antibacterial natural product abyssomicin C. Angewandte Chemie International Edition, 44, 6533–6536; (b) Nicolaou KC, Harrison ST (2006) Total synthesis of abyssomicin C and atrop-abyssomicin C. Angewandte Chemie International Edition, 45, 3256–3260; (c) Nicolaou KC, Harrison ST. (2007) Total synthesis of abyssomicin C, atrop-abyssomicin C, and abyssomicin D: Implications for natural origins of atrop-abyssomicin C. Journal of the American Chemical Society, 129, 429–440; (d) Nicolaou KC, Harrison ST, Chen JS. (2009) Discoveries from the abyss: The abyssomicins and their total synthesis. Synthesis, 33–42.
4.
For the first example of combination of enamine catalysis with π-allylpalladium complexes for the intermolecular alkylation of aldehydes, see: IbrahemI., CordovaA. (2006) Direct Catalytic Intermolecular α-Allylic Alkylation of Aldehydes by Combination of Transition-Metal and Organocatalysis. Angewandte Chemie International Edition, 45, 1952–1956.
5.
BihelovicF., MatovicR., VulovicB., SaicicR.N. (2007) Organocatalyzed cyclizations of π-allylpalladium complexes: A new method for the construction of five and six-membered rings. Organic Letters, 9, 5063–5066.
6.
(a) BihelovicF., SaicicR.N. (2012) Total synthesis of (-)-atrop-abyssomicin C, Angewandte Chemie International Edition, 51, 5687–5691; (b) Bihelovic F, Karadzic I, Matovic R and Saicic RN. (2013) Total synthesis and biological evaluation of (-)-atrop-abyssomicin C, Organic & Biomolecular Chemistry, 11, 5413–5424.
7.
For review articles on cooperative catalysis, see: (a) ShaoZ., ZhangH. (2009) Combining transition metal catalysis and organocatalysis: a broad new concept for catalysis. Chemical Society Reviews, 38, 2745–2755; (b) Zhong C, Shi X. (2010) When Organocatalysis Meets Transition-Metal Catalysis. European Journal of Organic Chemistry, 2999–3025; (c) Patil NT, Shinde VS, Gajula B. (2012) A one-pot catalysis: the strategic classification with some recent examples. Organic & Biomolecular Chemistry, 10, 211–224; (d) Du Z, Shao Z. (2013) Combining transition metal catalysis and organocatalysis – an update. Chemical Society Reviews, 42, 1337–1378; (e) Inamdar SM, Shinde VS, Patil NT (2015) Enantioselective cooperative catalysis. Organic & Biomolecular Chemistry, 13, 8116–8162; (f) Afewerki S, Cordova A. (2016) Combinations of Aminocatalysts and Metal Catalysts: A Powerful Cooperative Approach in Selective Organic Synthesis. Chemical Reviews, 116, 13512–13570.
8.
VulovicB., BihelovicF., MatovicR., SaicicR.N. (2009) Organocatalyzed Tsuji–Trost reaction: a new method for the closure of five- and six-membered rings. Tetrahedron, 65, 10485–10494.
9.
MurakamiS., TakemotoT., ShimizuZ. (1953) Studies on the effective principles of Digenea simplex Aq. Journal of the Pharmaceutical Society of Japan, 73, 1026–1028.
10.
For a review article on kainoids, see: ParsonsA.F. (1996) Recent developments in kainoid amino acid chemistry. Tetrahedron, 52, 4149–4174.
11.
For a review article on syntheses of allokainic acid, see: BhatC., KumarA. (2015) Synthesis of Allokainic acid: A review. Asian Journal of Organic Chemistry, 4, 102–115.
12.
LygoB., WainwrightP.G. (1997) A new class of asymmetric phase-transfer catalysts derived from Cinchona alkaloids — Application in the enantioselective synthesis of α-amino acids. Tetrahedron Letters, 38, 8595–8598.
13.
For the most recent books and selected reviews on gold-catalyzed reactions, see: (a) Gold Catalysis. An Homogeneous Approach. Catalytic Science Series, Vol. 13, TosteF.D., MicheletV., Eds.; Imperial College Press, Singapore, 2014; (b) Gagosz F.: Golden Opportunities in the Synthesis of Natural Products and Biologically Active Compounds. In Modern Tools for the Synthesis of Complex Bioactive Molecules, Cossy J, Arseniyadis S, Eds.; J. Wiley & Sons Inc., 2012, p. 111–154; (c) Pflästerer D, Hashmi SK. (2016) Gold catalysis in total synthesis – recent achievements. Chemical Society Reviews, 45, 1331–1367; (d) Fürstner A. (2014) From Understanding to Prediction: Gold- and Platinum-Based π-Acid Catalysis for Target Oriented Synthesis. Accounts of Chemical Research, 47, 925–938; (e) Ranieri B, Escofet I, Echavarren AE. (2015) Anatomy of gold catalysts: facts and myths. Organic & Biomolecular Chemistry, 13, 7103–7118; (f) Wang Y-M, Lackner AD, Toste FD. (2014) Development of Catalysts and Ligands for Enantioselective Gold Catalysis. Accounts of Chemical Research, 47, 889–901.
14.
(a) BuzasK., IstrateF.M., GagoszF. (2009) Gold-catalyzed rearrangement of propargylic tert-butyl carbonates. Tetrahedron, 65, 1889–1901; (b) Buzas K, Gagosz F. (2006) Gold(I)-Catalyzed Formation of 4-Alkylidene-1,3-dioxolan-2-ones from Propargylic tert-Butyl Carbonates. Organic Letters, 8, 515–518.
15.
When this research was underway, Li, Luo, Yang and collaborators reported the sequential cyclization of 1,7-diynes leading to exo-methylene cyclohexene derivatives, and applied it in several elegant syntheses: (a) ShiH., FangL., TanC., ShiL., ZhangW., LiC-C, LuoT., YangZ. (2011) Total Syntheses of Drimane-Type Sesquiterpenoids Enabled by a Gold-Catalyzed Tandem Reaction. Journal of the American Chemical Society, 133, 14944–14947. (b) Yue G, Zhang Y, Fang L, Li C-c, Luo T, Yang Z. (2014) Collective Synthesis of Cladiellins Based on the Gold-Catalyzed Cascade Reaction of 1,7-Diynes. Angewandte Chemie International Edition, 53, 1837–1840.
16.
Isolation and structure elucidation: (a) TatsutaK., TsuchiyaT., MikamiN., UmezawaS., UmezawaH., NaganawaH. (1974) KD16-U1, A new metabolite of streptomyces: isolation and structural studies. The Journal of Antibiotics, 27, 579–586; (b) Takeuchi T, Chimura H, Hamada M, Umezawa H, Yoshioka O, Oguchi N, Takahashi Y, Matsuda AJ. (1975) A glycoxalase I inhibitor of a new structural type produced by streptomyces. The Journal of Antibiotics, 28, 737–742; (c) Müller A, Keller-Schierlein W, Bielicki J, Rak G, Stümpfel J, Zähner H. (1986) Stoffwechselprodukte von Mikroorganismen. 237. Mitteilung. (2S, 3R, 4R, 6R)-2,3,4-Trihydroxy-6-methylcyclohexanon aus zwei Actinomyceten-Stämmen. Helvetica Chimica Acta, 69, 1829–1832.
17.
(a) For a review article on gabosines, see: MacD.H., ChandrasekharS., GreeR. (2012) Total Synthesis of Gabosines. European Journal of Organic Chemistry, 5881–5895; (b) For the first total synthesis of gabosine H, see: Prasad KR, Kumar SM. (2011) Total Synthesis of Gabosine H. Synlett, 1602–1604.
18.
FourriereG., LeclercE., QuirionJ-C, PannecouckeX.J. (2012) Synthesis of exo-methylenedifluorocyclopentanes as precursors of fluorinated carbasugars by 5-exo-dig radical cyclization. Journal of Fluorine Chemistry, 134, 172–179.
