The Structure Elucidation of Haprolid

Jun Li; Jun Xing; Daniel Lücke; Dennis Lübken; Lucas Millbrodt; Ruben R. Plentz; Markus Kalesse

doi:10.1055/s-0036-1591836

Synthesis, Inhaltsverzeichnis

Synthesis 2018; 50(03): 529-538
DOI: 10.1055/s-0036-1591836

feature

The Structure Elucidation of Haprolid

Autor*innen

Jun Li

^aLeibniz Universität Hannover, Institute for Organic Chemistry (OCI), Schneiderberg 1B, 30167 Hannover, Germany eMail: markus.kalesse@oci.uni-hannover.de

^bLeibniz Universität Hannover, Center for Biomolecular Drug Research (BMWZ), Schneiderberg 38, 30167 Hannover, Germany
Jun Xing

^cUniversitätsklinikum und Medizinische Fakultät Tübingen, Geissweg 3, 72076 Tübingen, Germany
Daniel Lücke

^aLeibniz Universität Hannover, Institute for Organic Chemistry (OCI), Schneiderberg 1B, 30167 Hannover, Germany eMail: markus.kalesse@oci.uni-hannover.de

^bLeibniz Universität Hannover, Center for Biomolecular Drug Research (BMWZ), Schneiderberg 38, 30167 Hannover, Germany
Dennis Lübken

^aLeibniz Universität Hannover, Institute for Organic Chemistry (OCI), Schneiderberg 1B, 30167 Hannover, Germany eMail: markus.kalesse@oci.uni-hannover.de

^bLeibniz Universität Hannover, Center for Biomolecular Drug Research (BMWZ), Schneiderberg 38, 30167 Hannover, Germany

^dHelmholtz-Zentrum für Infektionsforschung (HZI), Imhoffenstr. 7, 38124 Braunschweig, Germany
Lucas Millbrodt

^aLeibniz Universität Hannover, Institute for Organic Chemistry (OCI), Schneiderberg 1B, 30167 Hannover, Germany eMail: markus.kalesse@oci.uni-hannover.de

^bLeibniz Universität Hannover, Center for Biomolecular Drug Research (BMWZ), Schneiderberg 38, 30167 Hannover, Germany
Ruben R. Plentz

^cUniversitätsklinikum und Medizinische Fakultät Tübingen, Geissweg 3, 72076 Tübingen, Germany
Markus Kalesse *

^aLeibniz Universität Hannover, Institute for Organic Chemistry (OCI), Schneiderberg 1B, 30167 Hannover, Germany eMail: markus.kalesse@oci.uni-hannover.de

^bLeibniz Universität Hannover, Center for Biomolecular Drug Research (BMWZ), Schneiderberg 38, 30167 Hannover, Germany

^dHelmholtz-Zentrum für Infektionsforschung (HZI), Imhoffenstr. 7, 38124 Braunschweig, Germany

Abstract

Alle Artikel dieser Rubrik

Dedicated to Professor Cesare Gennari on the occasion of his 65^th birthday

Abstract

The assignment of two stereocenters of the natural product haprolid through the application of a profile hidden Markov model (HMM) and its confirmation through total synthesis of the natural product and of two of its diastereomers are reported. The structure elucidation of this polyketide-peptide hybrid natural product is a telling showcase of how difficult it can be to determine the absolute configuration of isolated stereocenters and the benefits of a gene cluster analysis for structure determination. The key steps of the synthesis are a selective epoxidation of a terminal olefin and the stereodivergent macrolactonization strategy. Furthermore, the biological evaluation of all products showed that all diastereomers are potent inhibitors of hepatocellular carcinoma cell lines.

Key words

hidden Markov model - structure elucidation - natural products - stereoselective synthesis - biological evaluation

Volltext

Referenzen

References
1 New address: Sandoz GmbH, Biochemiestraße 10, 6336 Langkampfen, Austria.
2 Herrmann J. Fayad AA. Müller R. Nat. Prod. Rep. 2017; 34: 135

3a Jahns C. Hoffmann T. Müller S. Gerth K. Washausen P. Höfle G. Reichenbach H. Kalesse M. Müller R. Angew. Chem. Int. Ed. 2012; 51: 5239 ; Angew. Chem. 2012, 124, 5330
3b Rentsch A. Kalesse M. Angew. Chem. Int. Ed. 2012; 51: 11381 ; Angew. Chem. 2012, 124, 11543
3c Hartmann O. Kalesse M. Angew. Chem. Int. Ed. 2014; 53: 7335 ; Angew. Chem. 2014, 126, 7463
3d Gieseler MT. Kalesse M. Org. Lett. 2014; 16: 548
3e Tautz T. Hoffmann J. Hoffmann T. Steinmetz H. Washausen P. Kunze B. Huch V. Kitsche A. Reichenbach H. Höfle G. Müller R. Kalesse M. Org. Lett. 2016; 18: 2560
3f Gerstmann L. Kalesse M. Chem. Eur. J. 2016; 32: 11210
3g Poock C. Kalesse M. Org. Lett. 2017; 19: 4536

4 Steinmetz H. Li J. Fu C. Zaburannyi N. Kunze B. Harmrolfs K. Schmitt V. Herrmann J. Reichenbach H. Höfle G. Kalesse M. Müller R. Angew. Chem. Int. Ed. 2016; 55: 10113 ; Angew. Chem. 2016, 128, 10267

5a Symkenberg G. Kalesse M. Angew. Chem. Int. Ed. 2014; 53: 1795 ; Angew. Chem. 2014, 126, 1825
5b Xiao Q. Young K. Zakarian A. J. Am. Chem. Soc. 2015; 137: 5907
5c Wang J. Chen S.-G. Sun B.-F. Lin G.-Q. Shang Y.-J. Chem. Eur. J. 2013; 19: 2539
5d Wang Y. O’Doherty G. J. Am. Chem. Soc. 2013; 135: 9334
5e Kong K. Enquist JA. Jr. McCallum ME. Smith GM. Matsumaru T. Menhaji-Klotz E. Wood JL. J. Am. Chem. Soc. 2013; 135: 10890
5f Holmes MT. Britton R. Chem. Eur. J. 2013; 19: 12649
5g Vadhadiya PM. Puranik VG. Ramana CV. J. Org. Chem. 2012; 77: 2169
5h Florence GJ. Wlochal J. Chem. Eur. J. 2012; 18: 14250

6 Janssen D. Abert D. Jansen R. Müller R. Kalesse M. Angew. Chem. Int. Ed. 2007; 46: 4898 ; Angew. Chem. 2007, 119, 4985
7 Brodmann T. Janssen D. Kalesse M. J. Am. Chem. Soc. 2010; 132: 13610
8 Reid R. Piagentini M. Rodriguez E. Ashley G. Viswanathan N. Carney J. Santi DV. Hutchinson CR. McDaniel R. Biochemistry 2003; 42: 72
9 Caffrey P. ChemBioChem 2003; 4: 654
10 Kitsche A. Kalesse M. ChemBioChem 2013; 14: 851

11a Lu H.-H. Raja A. Franke R. Landsberg D. Sasse F. Kalesse M. Angew. Chem. Int. Ed. 2013; 52: 1354 ; Angew. Chem. 2013, 125, 13791
11b Lu H.-H. Hinkelmann T. Tautz T. Li J. Sasse F. Franke R. Kalesse M. Org. Biomol. Chem. 2015; 13: 8029

12 Appel R. Angew. Chem., Int. Ed. Engl. 1975; 14: 801 ; Angew. Chem. 1975, 87, 863
13 Grignard V. C. R. Hebd. Seances Acad. Sci. 1900; 130: 1322

For the use of terpenes in polyketide synthesis, see:

14a Swatschek J. Grothues L. Bauer JO. Strohmann C. Christmann M. J. Org. Chem. 2014; 79: 976
14b Winter P. Swatschek J. Willot M. Radtke L. Olbrisch T. Schäfer A. Christmann M. Chem. Commun. 2011; 47: 12200

15 Winter P. Vaxelaire C. Heinz C. Christmann M. Chem. Commun. 2011; 47: 394
16 Colladon M. Scarso A. Sgarbossa P. Michelin RA. Strukul G. J. Am. Chem. Soc. 2006; 128: 14006
17 Bal BS. Childers WE. Pinnick HW. Tetrahedron 1981; 37: 2091
18 Shiina I. Kubota M. Oshiumi H. Hashizume M. J. Org. Chem. 2004; 69: 1822
19 Mitsunobu O. Synthesis 1981; 1