Abstract:[structure: see text]. A partial stereochemical assignment of quartromicins A3 (R = alpha-D-galactosyl) and D3 (R = H, M+ = Na+, K+, Ca+) is presented.
“…They display antiviral activity against herpes simplex virus type 1 (HSV-1), the influenza virus, and the human immunodeficiency virus (HIV). , Oki and co-workers 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. On the basis of published 1 H NMR data, supporting synthetic studies in our group, and consideration of possible biosynthetic precursors, we proposed the relative stereochemistry of quartromicins A 3 and D 3 depicted in Figure . 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. , 1 Structures of quartromicins A 3 and D 3 .…”
supporting
confidence: 58%
“…10 Treatment of 1 and dienophile 12a (R = i-Pr) with MeAlCl 2 at -78 °C for 5 d provided a 5 : 1 mixture cycloadducts 25a and 26a in 70% yield. Reduction of this mixture with LiAlH 4 and then oxidation of the resulting diols using the Parikh-Doering procedure 20 provided exohydroxy aldehyde 5 and the endo-diastereomer 4 in 60% combined yield. The spectroscopic data for 4 and 5 matched that for samples obtained from previous synthetic studies.…”
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...
“…They display antiviral activity against herpes simplex virus type 1 (HSV-1), the influenza virus, and the human immunodeficiency virus (HIV). , Oki and co-workers 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. On the basis of published 1 H NMR data, supporting synthetic studies in our group, and consideration of possible biosynthetic precursors, we proposed the relative stereochemistry of quartromicins A 3 and D 3 depicted in Figure . 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. , 1 Structures of quartromicins A 3 and D 3 .…”
supporting
confidence: 58%
“…10 Treatment of 1 and dienophile 12a (R = i-Pr) with MeAlCl 2 at -78 °C for 5 d provided a 5 : 1 mixture cycloadducts 25a and 26a in 70% yield. Reduction of this mixture with LiAlH 4 and then oxidation of the resulting diols using the Parikh-Doering procedure 20 provided exohydroxy aldehyde 5 and the endo-diastereomer 4 in 60% combined yield. The spectroscopic data for 4 and 5 matched that for samples obtained from previous synthetic studies.…”
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...
“…The tetronate antibiotics have been the focus of many recent biosynthetic research programs on account of their unusual polycyclic structures as well as their value as potential antimicrobial and antiproliferative agents. − A subclass of this family of natural products has drawn particular interest, because the tetronate or tetramate namesake appears to have undergone an intramolecular Diels–Alder reaction with a 1,3-diene to form a cyclohexene ring with a tertiary carbon joint. , Examples of such spirotetronates and spirotetramates are shown in Figure and include versipelostatin ( 74 ), − pyrroindomycin ( 75 ), − chlorothricin ( 76 ), − kijanimicin ( 77 ), − the quartromicins ( 78 ), − the abyssomicins ( 79 ), − tetrocarcin, − the lobophorins, − nomimicin, maklamicin, − and tetronothiodin. − Furthermore, several of these compounds also possess a second, decalin ring system, the formation of which is highly reminiscent of the reactions catalyzed by LovB and solanapyrone synthase (see above). Therefore, the pathways responsible for the biosynthesis of the spirotetronates and spirotetramates are unique, because many may involve not one but two enzyme-catalyzed Diels–Alder reactions.…”
Section: Spirotetronates and Spirotetramatesmentioning
[4 + 2]-Cycloadditions are increasingly being recognized in the biosynthetic pathways of many structurally complex natural products. A relatively small collection of enzymes from these pathways have been demonstrated to increase rates of cyclization and impose stereochemical constraints on the reactions. While mechanistic investigation of these enzymes is just beginning, recent studies have provided new insights with implications for understanding their biosynthetic roles, mechanisms of catalysis and evolutionary origin.
“…The characteristic tetrameric spirotetronate parts may be constructed via an intermolecular Diels-Alder reaction of the proposed monomer 34. [75][76][77][78][79] The stereochemistry of the quatromicins has recently been proposed based on the synthesis of the four possible isomers and extensive NMR analysis. The proposed structure contains two spirotetronate substructures which are epimeric at the spirotetronate centre.…”
Section: Intermolecular [4؉2] Adducts Via Type-i Pksmentioning
Recent studies on enzymes catalyzing the Diels- Alder reaction. often named "Diels-Alderases", clearlydemonstrated the involvement of this synthetically useful reaction in the biosynthesis of natural products.This review covers natural Diels-Alder type cycloadducts. synthetic efforts on the chemical feasibility ofthe biosynthctic Diels - Alder reaction and a brief history of studies on Diels-Alderases. In addition,reaction mechanisms of artificial and natural Diels--Alderases are discussed.
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