Studies on the Synthesis of Quartromicins A<sub>3</sub> and D<sub>3</sub>:  Synthesis of the Vertical and Horizontal Bis-Spirotetronate Fragments

Trullinger, Tony K.; Qi, Jun; Roush, William

doi:10.1021/jo061059c

Cited by 18 publications

(20 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…103a , 129 In addition, this group reported a strategy of connecting subunits 115 and 116 together using lithium halogen exchange and CeCl 3 coupling. 130 Bedel’s group offered an alternative strategy of constructing the spirotetronate subunits using RCM, but to date no total syntheses of quartromicins have been completed. 131 …”

Section: Synthetic Approaches Toward Spirotetronate Polyketidesmentioning

confidence: 99%

Spirotetronate Polyketides as Leads in Drug Discovery

Lacoske

Theodorakis

2014

J. Nat. Prod.

View full text Add to dashboard Cite

The discovery of chlorothricin (1) defined a new family of microbial metabolites with potent antitumor antibiotic properties collectively referred to as spirotetronate polyketides. These microbial metabolites are structurally distinguished by the presence of a spirotetronate motif embedded within a macrocyclic core. Glycosylation at the periphery of this core contributes to the structural complexity and bioactivity of this motif. The spirotetronate family displays impressive chemical structures, potent bioactivities, and significant pharmacological potential. This review groups the family members based on structural and biosynthetic considerations and summarizes synthetic and biological studies that aim to elucidate their mode of action and explore their pharmacological potential.

show abstract

Section: Synthetic Approaches Toward Spirotetronate Polyketidesmentioning

confidence: 99%

Spirotetronate Polyketides as Leads in Drug Discovery

Lacoske

Theodorakis

2014

J. Nat. Prod.

View full text Add to dashboard Cite

show abstract

“…The spectroscopic data for 4 and 5 matched that for samples obtained from previous synthetic studies. 5,7 These data demonstrate that dienophile 12a displays excellent diastereofacial selectivity and synthetically useful exo-selectivity in the Diels-Alder reaction with (Z)-substituted diene 1. Comparable selectivity was obtained when dienophile 12b (R = Me) was used, but the DielsAlder reaction was considerably less efficient in this case owing to the poor solubility of 12b at -78 °C.…”

Section: Nih Public Accessmentioning

confidence: 75%

Section: Nih Public Accessmentioning

confidence: 75%

Synthesis of Precursors of the Agalacto (Exo) Fragment of the Quartromicins via an Auxiliary-Controlled Exo-Selective Diels−Alder Reaction

Roush

2006

Org. Lett.

Self Cite

View full text Add to dashboard Cite

A direct synthesis of the α-hydroxyaldehyde exo-5, a precursor of the exo-spirotetronate subunit o f the quartromicins, was achieved through an exo-selective Lewis acid-catalyzed Diels-Alder reaction of dienophile 12a and diene 1.The quartromicins are a structurally unique group of spirotetronate natural products isolated in 1991 by Oki and co-workers. 1 They display antiviral activity against herpes simplex virus type 1 (HSV-1), influenza virus, and human immunodeficiency virus (HIV). 2,3 Oki and coworkers demonstrated that the quartromicins possess a unique 32-membered carbocyclic ring system containing two different spirotetronic acid units connected in an alternating head to tail manner. Based on published 1 H NMR data, 1 supporting synthetic studies in our group, 4 and consideration of possible biosynthetic precursors we proposed 5 the relative stereochemistry of quartromicins A 3 and D 3 depicted in Figure 1. We refer to the two spirotetronate fragments as endo (i.e., that bearing the galactose residue in quartromicin A 3 ) and exo (also referred to as the agalacto unit) by virtue of the Diels-Alder chemistry that has been targeted for their synthesis. 5,6We have previously reported syntheses of the enantiomerically pure monomeric endo (6) and exo (7) spirotetronate units of the quartromicins via the Diels-Alder reaction of (Z)-substituted diene 1 and the N-acryloyl sultam dienophile 2 (Figure 2). 5,6 The major (exo) product of this Diels-Alder reaction was converted to aldehyde exo-3, which was further elaborated to endo-α-hydroxy aldehyde 4 via a stereoselective two-step installation of the C-1 β-face hydroxyl group. 5 However, installation of the hydroxyl group on the hindered α-face of C-1, required for synthesis of exo-5, proved to be quite difficult and has been accomplished only via multistep sequences. 5,7 We therefore were interested in developing a more straightforward strategy that would allow hydroxyl group of exo-5 to be installed in many fewer steps, ideally during an exo-selective Diels-Alder reaction.Conformationally restricted (S)-cis enone and (S)-cis enoate dienophiles exhibit a striking preference for exo-Diels-Alder cycloaddition. 8 In previous studies, we have demonstrated that chiral dienophiles 8 and 9 (Figure 3) give excellent exo-and diastereofacial selectivity in thermal Diels-Alder reactions with a range of (E,E)-dienes. 8,9 However, dienophile 8 is not stable to the Lewis acidic reaction conditions required for the Diels-Alder coupling to the relatively unreactive (Z)-substituted diene 1. 10 While the chiral imide dienophile 9 underwent roush@scripps.edu. a MeAlCl 2 -catalyzed Diels-Alder reaction with 1 (data not shown), attempted manipulation of the major Diels-Alder product proved unproductive. 11 In addition, attempts to effect Lewisacid mediated Diels-Alder reations of 1 with α-substituted dienophiles 10 and 11 were unsuccessful. 5 The latter studies are consistent with literature reports that methacryloyl sultams adopt ground state conformations with the dienophil...

show abstract

“…The IMDA reaction is prevalent in almost every synthetic study of class II spirotetronates [81,83,84]. All these efforts toward class II spirotetronate aglycons are too cumbersome to practically bring forward large quantities of material, and they neglect the oligosaccharide chains, which are essential for biological activity in all marine-derived class II spirotetronates [85].…”

Section: Class II Marine Spirotetronatesmentioning

confidence: 99%

Marine Spirotetronates: Biosynthetic Edifices That Inspire Drug Discovery

Braddock

Theodorakis

2019

Marine Drugs

View full text Add to dashboard Cite

Spirotetronates are actinomyces-derived polyketides that possess complex structures and exhibit potent and unexplored bioactivities. Due to their anticancer and antimicrobial properties, they have potential as drug hits and deserve further study. In particular, abyssomicin C and tetrocarcin A have shown significant promise against antibiotic-resistant S. aureus and tuberculosis, as well as for the treatment of various lymphomas and solid tumors. Improved synthetic routes to these compounds, particularly the class II spirotetronates, are needed to access sufficient quantities for structure optimization and clinical applications.

show abstract

Studies on the Synthesis of Quartromicins A₃ and D₃: Synthesis of the Vertical and Horizontal Bis-Spirotetronate Fragments

Abstract: Syntheses of the vertical (3) and horizontal (4) bis-spirotetronate units of quartromicins A3 and D3 are described, along with an efficient synthesis of alpha-hydroxy aldehyde exo-8b, a precursor to the exo-spirotetronate fragments 19 and 21.

Cited by 18 publications

References 37 publications

Spirotetronate Polyketides as Leads in Drug Discovery

Spirotetronate Polyketides as Leads in Drug Discovery

Synthesis of Precursors of the Agalacto (Exo) Fragment of the Quartromicins via an Auxiliary-Controlled Exo-Selective Diels−Alder Reaction

Marine Spirotetronates: Biosynthetic Edifices That Inspire Drug Discovery

Contact Info

Product

Resources

About

Studies on the Synthesis of Quartromicins A3 and D3: Synthesis of the Vertical and Horizontal Bis-Spirotetronate Fragments

Abstract: Syntheses of the vertical (3) and horizontal (4) bis-spirotetronate units of quartromicins A3 and D3 are described, along with an efficient synthesis of alpha-hydroxy aldehyde exo-8b, a precursor to the exo-spirotetronate fragments 19 and 21.

Cited by 18 publications

References 37 publications

Spirotetronate Polyketides as Leads in Drug Discovery

Spirotetronate Polyketides as Leads in Drug Discovery

Synthesis of Precursors of the Agalacto (Exo) Fragment of the Quartromicins via an Auxiliary-Controlled Exo-Selective Diels−Alder Reaction

Marine Spirotetronates: Biosynthetic Edifices That Inspire Drug Discovery

Contact Info

Product

Resources

About

Studies on the Synthesis of Quartromicins A₃ and D₃: Synthesis of the Vertical and Horizontal Bis-Spirotetronate Fragments