Chemistry and Biology of Diazonamide A:  First Total Synthesis and Confirmation of the True Structure

Abstract

With the addition of a tenth ring, the exchange of an oxygen atom for a nitrogen in the heart of the molecule, and a different terminal residue, the revised architecture for diazonamide A (1) provided an even more challenging molecular puzzle for chemical synthesis than its predecessor. In this article, we detail the first successful total synthesis of diazonamide A, an endeavor which not only verified its proper connectivities and established the stereochemistry of its previously unassignable C-37 chiral center, but which also was attended by the development of several new synthetic strategies and tactics.

Atropselektive Synthese axial‐chiraler Biaryle

“…Kürzlich schlossen Nicolaou et al die erste Totalsynthese des komplexen polycyclischen Sekundärmetabolits Diazonamid A [117,118] ab (Schema 11, für einen alternativen Zugang siehe Schema 53). Ausgehend von dem verbrückten Arylbromid 84, das die chirale Information bereits enthielt, ergab die Wittkop-artige [119] Photocyclisierung das makrocyclische Biaryl (M)-85 als einziges Atrop-Diastereomer, wenn auch in mäßiger Ausbeute.…”

Total Synthesis of (±)-Dragmacidin E; Problems Solved and Lessons Learned

“…Indolic oxidation of the indole- N -unprotected tryptamine derivative 40 with DDQ followed by N -protection afforded the indolic ketone 41 in good yield. 16 Ketone reduction and subsequent azidation proceeded smoothly to give the indolic azide 42 . Attempts at this chemistry without first deactivating the indole nitrogen via BOC protection did not lead to any chemical reaction.…”

“…Unlike the simpler model systems (Schemes 6 and 7) where hydrogenolysis sufficed to convert azide to amine, the more complex azides 48 did not respond well to this chemistry. Fortunately, an alternative procedure based upon low-valent nickel 16 did perform satisfactorily, and so the route remained on track. N-BOC removal with TFA and conversion of the first-formed primary ammonium salt to the free amine with base set up the cyclocondensation to generate the dihydropyrazine-containing heptacyclic product 50 containing all of the rings of dragmacidin E. In some trials, 50 air-oxidized in part to the desired pyrazinone 51 , as evidenced by the development of the characteristic bright yellow color.…”

Towards the Synthesis of Massadine: A Unified Strategy for the Stereoselective Synthesis of the Carbocyclic C,D‐Ring Subunit

“…Upon screening for various conditions we were able to cleave the benzyl ethers using 20 equiv of boron trichloride in dichloromethane at À78 8C, which delivered diol 38 in 71 % yield (Scheme 8). [36] Activation of the hydroxyl groups for S N 2 displacement was realized by mesylation (98 %). Treatment of dimesylate 39 with sodium azide furnished a mixture of epimeric di-A C H T U N G T R E N N U N G azides.…”