The chemistry and biology of mycolactones
- Matthias Gehringer and
- Karl-Heinz Altmann
Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159
Graphical Abstract
Figure 1: Initial proposal for the core macrolactone structure (left) and the established complete structure ...
Figure 2: Mycolactone congeners and their origins.
Figure 3: Misassigned mycolactone E structure according to Small et al. [50] (11) and the correct structure (6) f...
Figure 4: Schematic illustration of Kishi’s improved mycolactone TLC detection method exploiting derivatizati...
Figure 5: Fluorescent probes derived from natural mycolactone A/B (1a,b) or its synthetic 8-desmethyl analogs...
Figure 6: Tool compounds used by Pluschke and co-workers for elucidating the molecular targets of mycolactone...
Figure 7: Synthetic strategies towards the extended mycolactone core. A) General strategies. B) Kishi’s appro...
Scheme 1: Kishi’s 1st generation approach towards the extended core structure of mycolactones. Reagents and c...
Scheme 2: Kishi’s 2nd generation approach towards the extended core structure of mycolactones. Reagents and c...
Scheme 3: Kishi’s 3rd generation approach towards the extended core structure of mycolactones. Reagents and c...
Scheme 4: Negishi’s synthesis of the extended core structure of mycolactones. Reagents and conditions: a) (i) ...
Scheme 5: Burkart’s (incomplete) 1st generation approach towards the extended core structure of mycolactones....
Scheme 6: Burkart’s (incomplete) 1st, 2nd and 3rd generation approach towards the extended mycolactone core s...
Scheme 7: Altmann’s synthesis of alkyl iodide 91. Reagents and conditions: a) (i) PMB-trichloroacetimidate, T...
Scheme 8: Final steps of Altmann’s synthesis of the extended core structure of mycolactones. Reagents and con...
Scheme 9: Basic principles of the Aggarwal lithiation–borylation homologation process [185,186].
Scheme 10: Aggarwal’s synthesis of the C1–C11 fragment of the mycolactone core. Reagents and conditions: a) Cl...
Scheme 11: Aggarwal’s synthesis of the linear C1–C20 fragment of the mycolactone core. Reagents and conditions...
Figure 8: Synthetic strategies towards the mycolactone A/B lower side chain.
Scheme 12: Gurjar and Cherian’s synthesis of the C1’–C8’ fragment of the mycolactone A/B pentaenoate side chai...
Scheme 13: Gurjar and Cherian’s synthesis of the benzyl-protected mycolactone A/B pentaenoate side chain. Reag...
Scheme 14: Kishi’s synthesis of model compounds for elucidating the stereochemistry of the C7’–C16’ fragment o...
Scheme 15: Kishi’s synthesis of the mycolactone A/B pentaenoate side chain. (a) (i) NaH, (EtO)2P(O)CH2CO2Et, T...
Scheme 16: Feringa and Minnaard's incomplete synthesis of mycolactone A/B pentaenoate side chain. Reagents and...
Scheme 17: Altmann’s approach towards the mycolactone A/B pentaenoate side chain. Reagents and conditions: a) ...
Scheme 18: Negishi’s access to the C1’–C7’ fragment of mycolactone A. Reagents and conditions: a) (i) n-BuLi, ...
Scheme 19: Negishi’s approach to the C1’–C7’ fragment of mycolactone B. Reagents and conditions: a) (i) DIBAL-...
Scheme 20: Negishi’s synthesis of the C8’–C16’ fragment of mycolactone A/B. Reagents and conditions: a) 142, BF...
Scheme 21: Negishi’s assembly of the mycolactone A and B pentaenoate side chains. Reagents and conditions: a) ...
Scheme 22: Blanchard’s approach to the mycolactone A/B pentaenoate side chain. a) (i) Ph3P=C(Me)COOEt, CH2Cl2,...
Scheme 23: Kishi’s approach to the mycolactone C pentaenoate side chain exemplified for the 13’R,15’S-isomer 1...
Scheme 24: Altmann’s (unpublished) synthesis of the mycolactone C pentaenoate side chain. Reagents and conditi...
Scheme 25: Blanchard’s synthesis of the mycolactone C pentaenoate side chain. Reagents and conditions: a) (i) ...
Scheme 26: Kishi’s synthesis of the tetraenoate side chain of mycolactone F exemplified by enantiomer 165. Rea...
Scheme 27: Kishi’s synthesis of the mycolactone E tetraenoate side chain. Reagents and conditions: a) (i) CH2=...
Scheme 28: Wang and Dai’s synthesis of the mycolactone E tetraenoate side chain. Reagents and conditions: a) (...
Scheme 29: Kishi’s synthesis of the dithiane-protected tetraenoate side chain of the minor oxo-metabolite of m...
Scheme 30: Kishi’s synthesis of the mycolactone S1 and S2 pentaenoate side chains. Reagents and conditions: a)...
Scheme 31: Kishi’s 1st generation and Altmann’s total synthesis of mycolactone A/B (1a,b) and Negishi’s select...
Scheme 32: Kishi’s 2nd generation total synthesis of mycolactone A/B (1a,b). Reagents and conditions: a) 2,4,6...
Scheme 33: Blanchard’s synthesis of the 8-desmethylmycolactone core. Reagents and conditions: a) (i) TsCl, TEA...
Scheme 34: Altmann’s (partially unpublished) synthesis of the C20-hydroxylated mycolactone core. Reagents and ...
Scheme 35: Altmann’s and Blanchard’s approaches towards the 11-isopropyl-8-desmethylmycolactone core. Reagents...
Scheme 36: Blanchard’s synthesis of the saturated variant of the C11-isopropyl-8-desmethylmycolactone core. Re...
Scheme 37: Structure elucidation of photo-mycolactones generated from tetraenoate 224.
Scheme 38: Kishi’s synthesis of the linear precursor of the photo-mycolactone B1 lower side chain. Reagents an...
Scheme 39: Kishi’s synthesis of the photo-mycolactone B1 lower side chain. Reagents and conditions: a) LiTMP, ...
Scheme 40: Kishi’s synthesis of a stabilized lower mycolactone side chain. Reagents and conditions: a) (i) TBD...
Scheme 41: Blanchard’s variation of the C12’,C13’,C15’ stereocluster. Reagents and conditions: a) (i) DIBAL-H,...
Scheme 42: Blanchard’s synthesis of aromatic mycolactone polyenoate side chain analogs. Reagents and condition...
Scheme 43: Small’s partial synthesis of a BODIPY-labeled mycolactone derivative and Demangel’s partial synthes...
Scheme 44: Blanchard’s synthesis of the BODIPY-labeled 8-desmethylmycolactones. Reagents and conditions: a) (i...
Scheme 45: Altmann’s synthesis of biotinylated mycolactones. Reagents and conditions: a) (i) CDI, THF, rt, 2 d...
Figure 9: Kishi’s elongated n-butyl carbamoyl mycolactone A/B analog.
