Due its unique structure and its reported potent antifungal activity, the marine polyketide hippolachnin A (1) has attracted much attention in the synthetic community. Herein, we describe the development of a concise, diversifiable and scalable synthesis of the racemic natural product, which serves as a platform for the generation of bioactive analogues. Biological testing of our synthetic material did not confirm the reported antifungal activity of hippolachnin A but unraveled moderate activity against nematodes and microbes.
Opportunistic infections by ubiquitous fungi represent a major challenge to immunocompromised patients. The basidiomycete yeast Cryptococcus neoformans, for instance, can cause life-threatening meningitis and affect the lungs and skin of patients with advanced acquired immunodeficiency syndrome (AIDS) [1,2,3,4,5,6]. Hippolachnin A (1) was recently isolated from the South China Sea sponge Hippospongia lachne. The molecule features six contiguous stereocenters embedded in a bicyclo[3.2.0]heptane framework, four of which bear ethyl groups. Biochemical assays, reported in the initial study, revealed high potency against several pathogenic fungi, including C. neoformans (MIC = 0.41 µM) . Biosynthetically, 1 is part of the plakortin family  and, more precisely, part of the gracilioether family (Fig. 1). This family also includes the unnamed compound 2, the presumptive biosynthetic precursor of 1, as well as the graciloethers (3, 5, 6), and plaktorin (4).
Attracted by its unusual structure combined with the potent bioactivity, numerous research groups, including ours, have developed unique synthetic solutions for this molecule. In the last three years, four total syntheses have been reported [9,10,11,12,13], including a recent biomimetic synthesis by Tang and Enders . In 2014, we launched a program to develop a scalable and diversifiable approach to hippolachnin A (1). Herein, we show how our strategy evolved, discuss our studies on synthetic derivatives, and the results of our evaluation of their biological properties.
Results and discussion
As outlined in Scheme 1, we initially focused on a strategy based non-biomimetic [2 + 2]-cycloaddition of allylic ester 8, to simultaneously form the cyclobutane and the tetrahydrofuran of the natural product. The vinylogous carbonate should then be installed by Peterson olefination. Even though the desired [2 + 2]-cycloaddition of an acyclic α,β-unsaturated ester was anticipated to be difficult, we envisioned that, conducting the reaction in an intramolecular fashion, might allow for efficient trapping of the photochemically formed triplet diradical.
The synthesis commenced with the preparation of tertiary alcohol 13 from dicyclopentadiene (9) (Scheme 2). Conjugate addition from the convex side of enone 10, obtained from Alder-ene reaction of 9 with singlet oxygen, afforded ketone 11 . Subsequent 1,2-addition of EtMgBr mediated by LaCl3.2LiCl yielded tertiary alcohol 12 as a single diastereoisomer . While initial attempts to effect thermolysis resulted in decomposition, flash vacuum pyrolysis (FVP) cleanly provided sensitive tertiary alcohol 13 in good yield .
With 13 in hand, we envisioned esterification with the known carboxylic acid 14 (Scheme 3) . Standard esterification conditions utilizing the acid chloride only resulted in isolation of the free acid after work up. Attempts to generate the acylium ion only led to decomposition of the starting materials . Anhydride 15 was found to be stable to column chromatography but could not be used for ester formation, even at elevated temperatures. Interestingly, both the acid chloride and the mixed anhydride were able to react with t-BuOK to form the corresponding t-butyl ester 16.
Since the sterical hindrance of the tertiary alcohol could not be overcome, we decided to install the fourth ethyl group at a later stage of the synthesis. The revised retrosynthesis is shown in Scheme 4. We envisioned formation of 1 by ethyl Grignard addition to cyclopentenone 17, followed by dehydration. The β-ketoester could be derived by Claisen condensation of methyl acetate with lactone 18. Lactone 18 would be traced back to an intramolecular [2 + 2]-cycloaddition of ester 19.
Epoxidation of cyclopentadiene  (20) followed by SN2׳ displacement with ethylcyanocuprate  provided allylic alcohol 21 in moderate yield (Scheme 5). Quantitative formation of the lithium alkoxide and subsequent quenching with acid chloride 14 gave rise to allylic ester 19.
With 19 in hand we investigated the key [2 + 2]-cycloaddition . Unfortunately, irradiation of 19 with 310 nm LEDs in the presence of either acetone or benzophenone in various solvents (MeCN, CH2Cl2, benzene) did not result in the desired cycloadditon. Instead, we isolated starting material as a mixture with its (E)-configured diastereomer 22. While excitation of the system proceeded smoothly as proved by the formation of 22, we wondered whether π-bond rotation was too fast to allow for capture of the diradical by the tethered olefin.
To prevent isomerization we decided to incorporate the enone double bond into a ring by stitching the ends of the ethyl groups together using a sulfur bridge. Ring expansion of tetrahydrothiopyranone 23 using ethyl diazoacetate gave rise to thiepanone 24 which, after reduction, mesylation, and elimination provided ethyl ester 26 . Saponification followed by activation of the carboxylic acid as the acid chloride and subsequent esterification accessed enoate 28 in moderate yields (Scheme 6). To investigate the cycloaddition, we submitted 28 to the same conditions used for 19. After irradiation, the clear solution became cloudy and NMR analysis of the mixture indicated decomposition of the starting material.
While excitation of the molecule was possible, no productive pathways were observed, which might be attributed to a preferred conformation of the molecule where both olefins are pointing into opposite directions. In order to provide the molecule more flexibility, β-ketoester 32 was prepared (Scheme 7). Activation of acid 30 with CDI and subsequent Claisen condensation with t-BuOAc, followed by ketalization, gave dioxanone 31 . Retro [4 + 2]-cycloaddition and trapping of the resulting ketene with alcohol 19 then afforded β-ketoester 32 . Irradiation of 32 under the previously established conditions resulted in a complex mixture from which we were unable to isolate the desired bicyclo[3.2.0]heptane 33.
Frustrated by our inability to effect (2 + 2) cycloadditons we decided to turn to a different type of photochemistry (Scheme 8). In our new retrosynthetic analysis, we planned to close the tetrahydofuran ring in 1 by O-alkylation of an enolized β-ketoester 34 . The vicinal ethyl groups should be introduced by addition of an ethyl nucleophile and an ethyl electrophile to the Michael acceptor 35. Compound 35 was derived from the known bicyclo[3.2.0]heptadiene 36, which can be obtained from tropolone ether 37 (Scheme 8) .
Our synthesis commences with the photochemical conversion of 37 into methoxy bicyclo[3.2.0]heptadienone 36, which was originally reported by Dauben et. al . Irradiation of 37 induced a disrotatory 4π-electrocyclization to give 38, which then undergoes an excited state rearrangement to yield 36. Notably, even though 38 is an isolatable intermediate, 36 was the only product obtained after full conversion of 37. Ethyl cuprate addition to 36 occurred exclusively from the convex side  of the molecule and gave, after Wittig olefination  and acid mediated cleavage of the enol ether  ketone 40 as a 10:1 mixture of E- and Z- isomers (major isomer shown). Formation of the vinyl triflate [30, 31] and subsequent carbomethoxylation  then gave methyl ester 41 (Scheme 9).
With 41 in hand, the stage was set for the installation of the vicinal ethyl groups (Scheme 10). We first envisioned the conjugate addition of an ethyl cuprate and subsequent alkylation at the α-position of the ester. While the conjugate addition occurred solely from the convex side of the molecule, acidic quenching of the resulting ester enolate gave an inconsequential mixture of diastereomers with respect to the ester group. Reformation of the enolate using LDA and subsequent trapping with ethyl iodide resulted in 2:1 mixture of diastereomers , favoring the desired one. We attributed this result to the opposing stereochemical bias provided by the bicyclic core and the newly introduced ethyl group. Although, the major isomer could be converted into an advanced intermediate 44 of the Wood-Brown synthesis , we thought that this low level of selectivity was unacceptable for an efficient synthesis.
To overcome this problem, we turned toward the 1,3-dipolar cycloaddition of a thiocarbonyl ylide followed by reductive desulfurization to add, in effect, two ethyl radicals across the strained and electron poor double bond of 41 [34,35,36,37,38]. The requisite thiocarbonyl ylide 48 could be generated in situ from sulfoxide 47 following Achiwa’s method [39,40,41,42,43,44]. Compound 47, in turn, was derived from (chloromethyl)trimethylsilane 45 by alkylation with methyl iodide followed by nucleophilic displacement with sodium sulfide and subsequent oxidation (Scheme 11).
Dropwise addition of 48 to a hot solution of 41 indeed resulted in the clean formation of tetrahydrothiophen 49, which was obtained as a single diastereosiomer. Single crystal X-ray structure analysis showed that the methyl groups adopt a trans-configuration with respect to the heterocyclic ring. Notably, the reaction also proceeds under high pressure conditions (12 kbar) at room temperature, albeit with slightly lower yield.
With the key intermediate in hand we turned our focus to the homologation of the ester group to the corresponding β-ketoester. Unfortunately, all attempts [45,46,47,48] to effect a Claisen condensation failed, presumably due to steric hinderance (Table 1).
We sought to overcome this problem by using a less hindered electrophile settling on the cyano group with its sp-hybridized carbon. To this end we prepared nitrile 52 from vinyl triflate 51 by Pd-catalyzed cross coupling with sodium cyanide  (Scheme 12). To our delight, the 1,3-dipolar cycloaddition gave tricycle 53 as a single diastereomer, albeit in slightly lower yield. Blaise reaction of 53 with zinc organyl 54 then yielded the desired en-amine 55 . Unfortunately, the vinylogous carbamate 55 proved to be completely resistant to hydrolysis with starting material recovered under standard conditions [51, 52]. Harsher conditions led to decomposition of 55.
Although methyl ester 41 was resistant to a crossed-Claisen condensation, it could be reduced to the primary alcohol and mildly reoxidized. The resulting aldehyde 56 was able to undergo an aldol addition  with the enolate generated from methyl acetate and gave, after Dess Martin oxidaition, the desired β-ketoester 56. Formation of the tin enolate followed by trapping of the simultaneously generated tertiary carbocation  gave rise to (Z)-configured vinylogous carbonate 57 . Its structure could be confirmed by X-ray structure analysis. Reductive desulfurization with Raney nickel in THF [55,56,57] gave access to the natural product, hippolachnin A, as a racemate (Scheme 13).
Piao et. al. reported strong antifungal activity of hippolachnin A . With a good synthetic entry at hand, we decided to develop analogues that would allow us to map structure-activity relationships and would show improved physicochemical properties. Since 1 is poorly soluble in aqueous solutions, we chose to synthesize more polar derivatives by oxidizing the sulfur of the advanced intermediate 57 to either the sulfoxide or the sulfone (Scheme 14). Notably, treatment of 57 with excess m-CPBA at room temperature led to partial isomerization of the double bond to afford a mixture of 58 and 59. Partial oxidation of 57 gave sulfoxide 60 as a 5:1 mixture of diastereomers. We also synthesized the butyrolactone 61 by acid mediated cyclization of 41.
With the racemic natural product and several synthetic analogous in hand, we evaluated the antifungal, antimicrobial and the nematicidal activity of 1, 57, 44, 61, 59, 58, and 60. We were surprised to find that (±)− 1 showed no antifungal activity, in particular against C. neoformans (Table 2). This observation was recently independently reported by Wood . It seems unlikely that the unnatural enantiomer somehow neutralizes the biological effect of (+)-hippolachnin A. Our synthetic analogs of 1 were also inactive against the fungi listed in Table 2, except for butyrolactone 61, which showed modest activity against C. neoformans. Compounds 1, 57, 44, and 61 exhibited weak antimicrobial activity (Table 2 and supporting information) and no or very weak cytotoxicity (supporting information). Interestingly, all analogs, including the natural product, inhibited the growth of Caenorhabditis elegans, but again with weak potency (Table 2).
Herein, we have presented the evolution of our campaign for the total synthesis of hippolachnin A. Starting from tropolone methyl ether 37, we developed a robust and scalable synthetic route which enabled us to synthesize not only more than 100 mg of the natural product but also a variety of synthetic derivatives. The bicyclic carbon core was constructed by photoisomerization of 37. The four ethyl groups were introduced by diastereoselective cuprate addition, Wittig olefination, and the 1,3-dipolar cycloaddition of a thiocarbonyl ylide. The latter represents a rarely used method to overcome steric hindrance and, in effect, link a nucleophile to an electrophile. The heterocyclic ring was closed via trapping of carbocation generated in situ by a tin enolate. Reports about the antifungal activity of hippolachnin A could not be confirmed. This is in keeping with several other recent cases where the purported bioactivity of natural products did not match the activity of their synthetic versions [59, 60]. Of course, this serves as yet another justification for total synthesis, which often provides material in purer form and on a larger scale than isolation from natural sources.
Dedicated to Prof. Samuel J. Danishefsky with admiration and gratitude.
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Kauffman CA. Cryptococcosis. In: Goldman L, Schafer AI, editors. Goldman-Cecil Medicine. 25th ed. Philadelphia: Elsevier Saunders; 2016: chap 336.
Govender NP, Patel J, van Wyk M, Chiller TM, Lockhart SR. Trends in antifungal drug susceptibility of Cryptococcus neoformans isolates obtained through population-based surveillance in South Africa in 2002–3 and 2007–8. Antimicrob Agents Chemother. 2011;55:2606–11.
Loyse A, et al. Cryptococcal meningitis: improving access to essential antifungal medicines in resource-poor countries. Lancet Infect Dis. 2013;13:629–37.
Sabiiti W, et al. Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis. J Clin Invest. 2014;124:2000–8.
Li SS, Mody CH. Cryptococcus. Ann Am Thorac Soc. 2010;7:186–96.
Hyde KD, Al-Hatmi A, Andersen B, Boekhout T, Buzina W, Dawson Jr TL, et al. The world’s ten most feared fungi. Fungal Divers 2018;93:161–94.
Piao SJ, et al. Hippolachnin A, a new antifungal polyketide from the South China Sea sponge Hippospongia lachne. Org Lett. 2013;15:3526–3529.
Rahm F, Harges PY, Kitching W. Metabolites from marine sponges of the genus Plakortis. Heterocycles. 2004;64:523–575.
Ruider SA, Sandmeier T, Carreira E-M. Total synthesis of (±)‐Hippolachnin A. Angew Chem Int Ed. 2015;54:2378–82.
McCallum ME, Rasik CM, Wood JL, Brown M-K. Collaborative Total synthesis: routes to (±)-Hippolachnin A enabled by quadricyclane cycloaddition and late-stage C–H oxidation. J Am Chem Soc. 2016;7:2437–42.
Datta R, Dixon RJ, Ghosh S. A convenient access to the tricyclic core structure of hippolachnin A. Tetrahedron Lett. 2016;57:29–31.
Xu ZJ, Wu Y. Efficient synthetic routes to (±)‐Hippolachnin A, (±)‐Gracilioethers E and F and the alleged structure of (±)‐Gracilioether I. Chem Eur J. 2017;23:2026–30.
Winter N, Trauner D. Thiocarbonyl Ylide chemistry enables a concise synthesis of (±)-Hippolachnin A. J Am Chem Soc. 2017;139:11706–9.
Li Q, et al. Enantioselective total syntheses of (+)-Hippolachnin A, (+)-Gracilioether A, (−)-Gracilioether E, and (−)-Gracilioether F. J Am Chem Soc. 2018;140:1937–44.
Demuynck ALW, et al. Retro‐diels–alder reactions of masked cyclopentadienones catalyzed by heterogeneous brønsted acids. Adv Synth Catal. 2010;352:3419–30.
Krasovskiy A, Kopp F, Knochel P. Soluble lanthanide salts (LnCl3·2 LiCl) for the Improved addition of organomagnesium reagents to carbonyl compounds. Angew Chem Int Ed Engl. 2006;45:497–500.
Zhu J, Yang J-Y, Klunder AJH, Liu Z-Y, Zwanenburg B. A stereo- and enantioselective approach to clavulones from tricyclodecadienone using flash vacuum thermolysis. Tetrahedron. 1995;51:5847–70.
Zweifel G, Steele RB. A new and convenient method for the preparation of isomerically pure alpha-beta-unsaturated derivatives via hydroalumination of alkynes. J Am Chem Soc. 1967;89:2754–5.
Effenberger F, Epple F, Eberhard JK, Bühler U, Sohn E. Carbonsäure‐trifluormethansulfonsäure‐ und ‐methansultonsäure‐anhydride, Darstellung und Dissoziationstendenz. Chem Ber. 1983;116:1183–94.
M Korach, DR Nielsen, WH Rideout, Cyclopentenediol. Org Synth. 1962,42:50.
Kobayashi Y, Ito M, Igarashi J. Alkylation of 4-substituted 1-acetoxy-2-cyclopentenes by using copper reagents derived from alkylmagnesium halides and copper(I) cyanide. Tetrahedron Lett. 2002;43:4829–32.
Reichardt C. Solvents and Solvent Effects in Organic Chemistry. Weinheim: VCH; 1988.
Zhou T, Peters B, Maldonado MF, Govender T, Andersson PG. Enantioselective synthesis of chiral sulfones by ir-catalyzed asymmetric hydrogenation: a facile approach to the preparation of chiral allylic and homoallylic compounds. J Am Chem Soc. 2012;134:13592–5.
Chen J, Chen J, Xie Y, Zhang H. Enantioselective total synthesis of (−)‐stenine. Angew Chem Int Ed. 2012;51:1024–7.
Palma A, Serginson JM, Barrett AG. Synthesis of poly β ketoesters via double acylketene trapping. Tetrahedron Lett. 2015;56:674–6.
Reetz MT, Chatziiosifidis I, Schwellnus K. Allgemeines Verfahren zur intramolekularen α‐tert‐Alkylierung von Carbonylverbindungen. Angew Chem. 1981;93:716–17.
Dauben W-G, Koch K, Smith S-L-, Chapman O-L. Photoisomerizations in the α-tropolone series: the mechanistic path of the α-tropolone methyl ether to methyl 4-Oxo-2-cyclopentenylacetate Conversion. J Am Chem Soc. 1963;85:2616–21.
Barbasiewicz M, Michalak M, Grela K. A new family of halogen‐chelated Hoveyda–Grubbs‐type metathesis. Catal Chem Eur J. 2012;18:14237–41.
Stille JR, Santarsiero BD, Grubbs RH. Rearrangement of bicyclo[2.2.1]heptane ring systems by titanocene alkylidene complexes to bicyclo[3.2.0]heptane enol ethers. Total synthesis of (. + −)-.DELTA.9(12)-capnellene. J Org Chem. 1990;55:843–62.
Bonnaud B, Mariet N, Vacher B. Preparation of conformationally constrained α2‐antagonists: the bicyclo[3.2.0]heptane approach. Eur J Org Chem. 2006; 246–56.
Molander GA, Carey JS. Total synthesis of furanether B. An application of a [3 + 4] annulation strategy. J Org Chem. 1995;60:4845–9.
Magauer T, Mulzer J, Tiefenbacher K. Total syntheses of (+)-echinopine A and B: determination of absolute stereochemistry. Org Lett. 2009;11:5306–9.
Meier R, Trauner D. A synthesis of (±)‐plydactone. Angew Chem Int Ed. 2016;55:11251–5.
Huisgen R, Mloston G, Polborn K, Sustmann R. 1,3‐dithiolanes from cycloadditions of alicyclic and aliphatic thiocarbonyl ylides with thiones: regioselectivity. Chem Eur J. 2003;9:2256–63.
Huisgen R, Kalvinsch I, Li X, Mloston, G. The formation of 1,3‐dithiolanes from aromatic thioketones and diazomethane—the mechanism of the schönberg reaction. Eur J Org Chem. 2000; 1685–94.
Kellogg RM. The molecules R2CXCR2 including azomethine, carbonyl and thiocarbonyl ylides. Their syntheses, properties and reactions. Tetrahedron. 1976;32:2165–84.
Hosomi A, Matsuyama Y, Sakurai H. Chloromethyl trimethylsilylmethyl sulphide as a parent thiocarbonyl ylide synthon. A simple synthesis of dihydro- and tetrahydro-thiophenes. J Chem Soc, Chem Commun. 1986; 1073–4.
Lan Y, Houk KN. Mechanism and stereoselectivity of the stepwise 1,3-dipolar cycloadditions between a thiocarbonyl ylide and electron-deficient dipolarophiles: a computational investigation. J Am Chem Soc. 2010;132:17921–7.
Terao Y, Tanaka M, Imai N, Achiwa K. New generation of thiocarbonyl ylide and its 1,3-cycloaddition leading to tetrahydrothiophene derivatives. Tetrahedron Lett. 1985;25:3011–4.
Terao Y, Aono M, Imai N, Achiwa K. Thiocarbonyl ylides. VI. New generation of thiocarbonyl ylides from organosilicon compounds containing sulfur and their 1,3-cycloadditions. Chem Pharm Bull. 1987;35:1734–40.
Terao Y, Aono I, Takahashi I, Achiwa K. Generation of Thioketene s-methylides and their 1,3-cycloadditions. Chem Lett. 1986;15:2089–92.
Aono M, Terao Y, Achiwa K. New method for generation of Thiocarbonyl Ylides from Bis(trimethylsilylmethyl)sulfoxides and their application to cycloadditions. Heterocycles . 1995;40:249–60.
Cherney RJ, et al. Conversion of potent MMP inhibitors into selective TACE inhibitors. Bioorg Med Chem Lett. 2006;16:1028–31.
Aono M, Hyodo C, Terao Y, Achiwa K. Generation of thiocarbonyl ylides with release of disiloxane from bis(trimethylsilylmethyl) sulfoxides. Tetrahedron Lett. 1986;27:4039–42.
Frostic FF Jr, Hauser C. Condensations of Esters by Diisopropylaminomagnesium Bromide and Certain Related Reagents. J Am Chem Soc. 1949;71:1350–2.
Stoll I, Flament M. Synthèse du « Propylure », phéromone sexuelle de Pectinophora gossypiella SAUNDERS. Helv Chim Acta. 1969;52:1996–2003.
Lehmann F, Holm M, Laufer S. Three-component combinatorial synthesis of novel dihydropyrano[2,3-c]pyrazoles. J Comb Chem. 2008;10:364–7.
Komine K, Nomura Y, Ishihara J, Hatakeyama S. Total synthesis of (−)-N-Methylwelwitindolinone C isothiocyanate based on a Pd-catalyzed tandem enolate coupling strategy. Org Lett. 2015;17:3918–21.
Kou KGM, et al. Syntheses of denudatine diterpenoid alkaloids: cochlearenine, N-Ethyl-1α-hydroxy-17-veratroyldictyzine, and paniculamine. J Am Chem Soc. 2016;138:10830–3.
Mineno M, Sawai Y, Kanno K, Sawada N, Mizufune H. Double reformatsky reaction: divergent synthesis of δ-hydroxy-β-ketoesters. J Org Chem. 2013;78:5843–5850.
Stamhuis EJ, Maas W. Mechanism of enamine reactions. II.1 The hydrolysis of tertiary enamines. J Org Chem. 1965;30:2156–60.
Maas W, Janssen MJ, Stamhuis EJ, Wynberg H. Mechanism of enamine reactions. IV. The hydrolysis of tertiary enamines in acidic medium. J Org Chem. 1967;32:1111–5.
Van der Veen R-H, Geenevasen J-A-J, Cerfontain H. Reactions of α-aryl carbonyl compounds with lithium ester enolates. Can J Chem. 1984;62:2202–5.
Hanquet G, Salom-Roig XJ, Lemeitour S, Solladie G. Isomerisation of (E)‐2‐tetrahydrofurylidenealkanecarboxylic Esters and amides into their (Z) isomers by chelation control with metallated bases or Lewis acids. Eur J Org Chem. 2002; 2112–9.
Lin R, Cao L, West FG. Medium-sized cyclic ethers via stevens [1,2]-shift of mixed monothioacetal-derived sulfonium ylides: application to formal synthesis of (+)-laurencin. Org Lett. 2017;19:552–5.
Hauptmann H, Walter WF. The action of raney nickel on organic sulfur compounds. Chem Rev. 1962;62:347–404.
Rentner J, Kljajic M, Offner L, Breinbauer R. Recent advances and applications of reductive desulfurization in organic synthesis. Tetrahedron 2014;70:8983–9027.
Timmerman JC, Wood JL. Synthesis and biological evaluation of hippolachnin A analogues. Org Lett. 2018;20:3788–92.
Cernijenko A, Risgaard R, Baran PS. 11-step total synthesis of (−)-maoecrystal V. J Am Chem Soc. 2016;138:9425–9428.
Tian M, Yan M, Baran PS. 11-step total synthesis of araiosamines. J Am Chem Soc. 2016;138:14234–14237.
Rupcic Z, Chepkirui C, Hernández-Restrepo M, Crous PW, Luangsa-ard JJ, Stadler M. New nematicidal and antimicrobial secondary metabolites from a new species in the new genus, Pseudobambusicola thailandica. MycoKeys. 2018;33:1–23.
We would like to thank Dr. Peter Mayer for X-ray structure analysis. Additionally, we would like to acknowledge the Deutsche Forschungsgemeinschaft (SFB 749 and CIPSM) for generous funding.