{ "document_id": 14408, "page": 4, "width_pt": 612, "height_pt": 792, "rotation": 0, "pipeline_version": "paddleocr-vl-1.6+paul-48", "engine": "paddleocr_vl", "source_run_id": 14519, "item_count": 72, "counts_by_type": { "formula": 1, "header": 3, "heading": 2, "text": 66 }, "build_ms": 10, "items": [ { "id": "p4.1", "order": 1, "type": "header", "bbox": { "l": 53.52, "t": 766.08, "r": 112.32, "b": 755.76 }, "text": "Invited Review", "attrs": { "block_label": "header" }, "level": 2 }, { "id": "p4.2", "order": 2, "type": "header", "bbox": { "l": 349.92, "t": 766.08, "r": 540.24, "b": 756 }, "text": "Journal of Natural Products, 1999, Vol. 62, No. 3", "attrs": { "block_label": "header" }, "level": 2 }, { "id": "p4.3", "order": 3, "type": "header", "bbox": { "l": 543.12, "t": 765.84, "r": 558.72, "b": 756.72 }, "text": "507", "attrs": { "block_label": "number" }, "level": 2 }, { "id": "p4.4", "order": 4, "type": "text", "bbox": { "l": 51.6, "t": 745.68, "r": 296.4, "b": 546.48 }, "text": "epimerized upon treatment with weak base.[p4.4.1] The two resulting C-36C-34 epimers have identical MS, [p4.4.2]H and [p4.4.3]C NMR, IR, and UV spectra. However, determination of the specific rotation of the mixtures and enzymatic oxidation after chemical degradation, have allowed characterization of these epimers. To determine the absolute stereochemistry at the C-36 or C-34 centers of such Annonaceous acetogenins, comparison by circular dichroism is used;[p4.4.4] thus, basic conditions must be avoided in extraction, fractionation, and isolation to preserve the natural integrity of the [p4.4.5]-lactone. HPLC detection of NADH released from the enzymatic oxidation of L- or D-lactic acid, obtained by the cleavage of the terminal [p4.4.6]-unsaturated [p4.4.7]-methyl- [p4.4.8]-lactone, to pyruvic acid by lactate dehydrogenase was used to quantify the epimerization chemically.[p4.4.9] To date, with more than 350 acetogenins isolated, all of the natural Annonaceous acetogenins, except when so epimerized, possess the S absolute configuration at their C-36 or C-34 positions.", "children": [ { "id": "p4.4.1", "order": 5, "type": "text", "bbox": { "l": 51.6, "t": 745.68, "r": 296.4, "b": 546.48 }, "text": "⁶³", "attrs": { "inline": true, "text_offset": 41, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.4.2", "order": 6, "type": "text", "bbox": { "l": 51.6, "t": 745.68, "r": 296.4, "b": 546.48 }, "text": "¹", "attrs": { "inline": true, "text_offset": 104, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.4.3", "order": 7, "type": "formula", "bbox": { "l": 51.6, "t": 745.68, "r": 296.4, "b": 546.48 }, "text": "¹³", "attrs": { "latex": "{}^{13}", "inline": true, "text_offset": 118, "text_span": 8, "bbox_estimated": true, "alt": "to the power of 13", "mathml": "13" } }, { "id": "p4.4.4", "order": 8, "type": "text", "bbox": { "l": 51.6, "t": 745.68, "r": 296.4, "b": 546.48 }, "text": "³⁴", "attrs": { "inline": true, "text_offset": 461, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.4.5", "order": 9, "type": "text", "bbox": { "l": 51.6, "t": 745.68, "r": 296.4, "b": 546.48 }, "text": "γ", "attrs": { "inline": true, "text_offset": 594, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.4.6", "order": 10, "type": "text", "bbox": { "l": 51.6, "t": 745.68, "r": 296.4, "b": 546.48 }, "text": "α,β", "attrs": { "inline": true, "text_offset": 738, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.4.7", "order": 11, "type": "text", "bbox": { "l": 51.6, "t": 745.68, "r": 296.4, "b": 546.48 }, "text": "γ", "attrs": { "inline": true, "text_offset": 759, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.4.8", "order": 12, "type": "text", "bbox": { "l": 51.6, "t": 745.68, "r": 296.4, "b": 546.48 }, "text": "γ", "attrs": { "inline": true, "text_offset": 776, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.4.9", "order": 13, "type": "text", "bbox": { "l": 51.6, "t": 745.68, "r": 296.4, "b": 546.48 }, "text": "⁶⁴", "attrs": { "inline": true, "text_offset": 885, "text_span": 8, "bbox_estimated": true } } ] }, { "id": "p4.5", "order": 14, "type": "text", "bbox": { "l": 51.6, "t": 545.28, "r": 296.16, "b": 439.68 }, "text": "Shi et al. have successfully applied the Mosher ester method to determine the absolute stereochemistry at 1,2-vicinal diols.[p4.5.1] This method uses only small amounts of material that are sufficient to achieve the per-Mosher esters. They observed that the cancellation/enforcement effect of overlapping MPTA planes could still be analyzed and utilized to predict the absolute stereochemistry of the 1,2-vicinal diol compounds, assuming that MPTA groups could still freely rotate, in the long aliphatic chain, and preserve their ideal conformations.", "children": [ { "id": "p4.5.1", "order": 15, "type": "text", "bbox": { "l": 51.6, "t": 545.28, "r": 296.16, "b": 439.68 }, "text": "⁶⁵", "attrs": { "inline": true, "text_offset": 124, "text_span": 8, "bbox_estimated": true } } ] }, { "id": "p4.6", "order": 16, "type": "text", "bbox": { "l": 51.84, "t": 438.48, "r": 296.16, "b": 249.84 }, "text": "Alali et al. have tabulated interesting observations on the chemical shift differences of 1,3-diols.[p4.6.1] A pseudothreo or -erythro spatial relationship can be easily deduced by analyzing the [p4.6.2]H and [p4.6.3]C NMR chemical shift differences of the carbinol centers in comparison with an isolated hydroxyl group at a carbinol center in a long chain. In comparison with an isolated hydroxyl oxymethine along a hydrocarbon chain, hydroxyl oxymethines of 1,3-pseudo-threo diols usually experience downfield shifts ca. +0.32 ppm in the [p4.6.4]H NMR spectrum and an upfield chemical shift of ca. -28 ppm in the [p4.6.5]C NMR spectrum. On the other hand, 1,3-pseudoerythro diols usually experience a downfield chemical shift of ca. +0.32 ppm and ca. +0.50 ppm in both the [p4.6.6]H and [p4.6.7]C NMR spectra, respectively. Accordingly, it can be predicted that tonkinin A, tonkinin B, tonkinesin A, and tonkinesin B all have a pseudothreo relationship between their carbinol centers at C-15 and C-17. [p4.6.8]", "children": [ { "id": "p4.6.1", "order": 17, "type": "text", "bbox": { "l": 51.84, "t": 438.48, "r": 296.16, "b": 249.84 }, "text": "¹⁰", "attrs": { "inline": true, "text_offset": 100, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.6.2", "order": 18, "type": "text", "bbox": { "l": 51.84, "t": 438.48, "r": 296.16, "b": 249.84 }, "text": "¹", "attrs": { "inline": true, "text_offset": 195, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.6.3", "order": 19, "type": "text", "bbox": { "l": 51.84, "t": 438.48, "r": 296.16, "b": 249.84 }, "text": "¹³", "attrs": { "inline": true, "text_offset": 209, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.6.4", "order": 20, "type": "text", "bbox": { "l": 51.84, "t": 438.48, "r": 296.16, "b": 249.84 }, "text": "¹", "attrs": { "inline": true, "text_offset": 540, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.6.5", "order": 21, "type": "text", "bbox": { "l": 51.84, "t": 438.48, "r": 296.16, "b": 249.84 }, "text": "¹³", "attrs": { "inline": true, "text_offset": 615, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.6.6", "order": 22, "type": "text", "bbox": { "l": 51.84, "t": 438.48, "r": 296.16, "b": 249.84 }, "text": "¹", "attrs": { "inline": true, "text_offset": 775, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.6.7", "order": 23, "type": "text", "bbox": { "l": 51.84, "t": 438.48, "r": 296.16, "b": 249.84 }, "text": "¹³", "attrs": { "inline": true, "text_offset": 789, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.6.8", "order": 24, "type": "text", "bbox": { "l": 51.84, "t": 438.48, "r": 296.16, "b": 249.84 }, "text": "^{10,66}", "attrs": { "inline": true, "text_offset": 1004, "text_span": 8, "bbox_estimated": true } } ] }, { "id": "p4.7", "order": 25, "type": "heading", "bbox": { "l": 52.32, "t": 239.76, "r": 102.24, "b": 228.48 }, "text": "Synthesis", "attrs": { "block_label": "paragraph_title" }, "level": 3 }, { "id": "p4.8", "order": 26, "type": "text", "bbox": { "l": 51.6, "t": 222.72, "r": 296.4, "b": 33.12 }, "text": "Due to the waxy nature of the Annonaceous acetogenins, X-ray crystallography is difficult, and definite stereochemical assignments are not easily made. Since the discovery of the first acetogenin, uvaricin, in 1982, which was published without any stereochemical assignments of its seven stereocenters, it was obvious that synthetic models were urgently needed to aid the complete structural elucidations of these multi-stereocentered compounds.7 Several synthetic models, especially those that do not require derivatization, have been proven to be very helpful in predicting the relative stereochemistry of the THF ring systems, with their flanking hydroxyls, and of the 4-hydroxylated [p4.8.1]-lactone.58–60,62 Additional synthetic models are still needed to predict the relative stereochemistry of several of the expanding new types of acetogenins, e.g., the hydroxylated-THP compounds, tri-THF compounds, and the bis-THF compounds with one flanking hydroxyl, and these models could be logical targets for further syntheses.\nThe potent and diverse bioactivities of Annonaceous acetogenins have recently caught the eye of many groups of synthetic chemists.[p4.8.2] Convergent strategies are usually chosen to synthesize these compounds. These are based on the coupling of a THF ring core and a terminal [p4.8.3]-lactone synthon. To achieve the specific stereochemistry, either chiral starting materials ( [p4.8.4]-amino acids, sugars) or some asymmetric reactions using chiral catalysts (Sharpless epoxidation, Sharpless dihydroxylation) are employed.", "children": [ { "id": "p4.8.1", "order": 27, "type": "text", "bbox": { "l": 51.6, "t": 222.72, "r": 296.4, "b": 33.12 }, "text": "γ", "attrs": { "inline": true, "text_offset": 687, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.8.2", "order": 28, "type": "text", "bbox": { "l": 51.6, "t": 222.72, "r": 296.4, "b": 33.12 }, "text": "^{2-4,67-69}", "attrs": { "inline": true, "text_offset": 1158, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.8.3", "order": 29, "type": "text", "bbox": { "l": 51.6, "t": 222.72, "r": 296.4, "b": 33.12 }, "text": "γ", "attrs": { "inline": true, "text_offset": 1305, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.8.4", "order": 30, "type": "text", "bbox": { "l": 51.6, "t": 222.72, "r": 296.4, "b": 33.12 }, "text": "α", "attrs": { "inline": true, "text_offset": 1407, "text_span": 8, "bbox_estimated": true } } ] }, { "id": "p4.9", "order": 31, "type": "text", "bbox": { "l": 314.64, "t": 745.44, "r": 559.2, "b": 651.36 }, "text": "The potent and diverse bioactivities of Annonaceous acetogenins have recently caught the eye of many groups of synthetic chemists.[p4.9.1] Convergent strategies are usually chosen to synthesize these compounds. These are based on the coupling of a THF ring core and a terminal [p4.9.2]-lactone synthase. To achieve the specific stereochemistry, either chiral starting materials ( [p4.9.3]-amino acids, sugars) or some asymmetric reactions using chiral catalysts (Sharpless epoxidation, Sharpless dihydroxylation) are employed.", "children": [ { "id": "p4.9.1", "order": 32, "type": "text", "bbox": { "l": 314.64, "t": 745.44, "r": 559.2, "b": 651.36 }, "text": "^{2-4,67-69}", "attrs": { "inline": true, "text_offset": 130, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.9.2", "order": 33, "type": "text", "bbox": { "l": 314.64, "t": 745.44, "r": 559.2, "b": 651.36 }, "text": "γ", "attrs": { "inline": true, "text_offset": 277, "text_span": 8, "bbox_estimated": true } }, { "id": "p4.9.3", "order": 34, "type": "text", "bbox": { "l": 314.64, "t": 745.44, "r": 559.2, "b": 651.36 }, "text": "α", "attrs": { "inline": true, "text_offset": 380, "text_span": 8, "bbox_estimated": true } } ] }, { "id": "p4.10", "order": 35, "type": "text", "bbox": { "l": 314.4, "t": 650.4, "r": 559.68, "b": 450.48 }, "text": "Kienan et al. successfully synthesized goniocin[p4.10.1] and cyclogoniodenin T[p4.10.2] and its unique tri-THF stereoisomer, 17,18bis-epi-goniocin, using tandem cyclization with rhenium oxide.[p4.10.3] Inspired by Hoye's work, Kienan et al. also synthesized mucocin, the first THP-bearing acetogenin, using all-trans-1,5,9-cyclododecatriene, and they completed the synthesis in 20 steps.[p4.10.4] This work confirmed our proposed relative as well as absolute stereochemistry of mucocin and, also, added credibility both to Born's rule,[p4.10.5] in being able to predict the relative stereochemistry of the hydroxyl-flanked THP ring as well as the hydroxyl-flanked THF ring, and to the intramolecular formaldehyde closure reaction,[p4.10.6] in facilitating the absolute stereochemical assignments of closely located carbinol centers. As demonstrated by their total synthesis of trilobacin, Kienan et al. designed an efficient convergent synthetic strategy that provided a useful entry to a 32-membered chemical library of stereoisomeric bis-THF acetogenins.[p4.10.7] Thus, combinatorial chemistry has been applied in this field.", "children": [ { "id": "p4.10.1", "order": 36, "type": "text", "bbox": { "l": 314.4, "t": 650.4, "r": 559.68, "b": 450.48 }, "text": "⁴⁶", "attrs": { "inline": true, "text_offset": 47, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.10.2", "order": 37, "type": "text", "bbox": { "l": 314.4, "t": 650.4, "r": 559.68, "b": 450.48 }, "text": "⁴⁸", "attrs": { "inline": true, "text_offset": 78, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.10.3", "order": 38, "type": "text", "bbox": { "l": 314.4, "t": 650.4, "r": 559.68, "b": 450.48 }, "text": "^{50,51}", "attrs": { "inline": true, "text_offset": 192, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.10.4", "order": 39, "type": "text", "bbox": { "l": 314.4, "t": 650.4, "r": 559.68, "b": 450.48 }, "text": "⁷⁰", "attrs": { "inline": true, "text_offset": 387, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.10.5", "order": 40, "type": "text", "bbox": { "l": 314.4, "t": 650.4, "r": 559.68, "b": 450.48 }, "text": "⁵⁹", "attrs": { "inline": true, "text_offset": 535, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.10.6", "order": 41, "type": "text", "bbox": { "l": 314.4, "t": 650.4, "r": 559.68, "b": 450.48 }, "text": "⁷¹", "attrs": { "inline": true, "text_offset": 730, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.10.7", "order": 42, "type": "text", "bbox": { "l": 314.4, "t": 650.4, "r": 559.68, "b": 450.48 }, "text": "⁷²", "attrs": { "inline": true, "text_offset": 1056, "text_span": 9, "bbox_estimated": true } } ] }, { "id": "p4.11", "order": 43, "type": "text", "bbox": { "l": 314.4, "t": 450.24, "r": 559.68, "b": 355.68 }, "text": "A noteworthy strategy is the efficient bidirectional synthetic approach to the C-2 symmetric stereoisomers of 2,2-bis-THF acetogenins as reported by Marshall et al. in the last two years. [p4.11.1]Utilizing[p4.11.2], [p4.11.3]-dioxygenated dialdehyde and a nonracemic [p4.11.4]- or [p4.11.5]-oxygenated allylic stannane, they were able to synthesize (+)-asimicin, asiminocin, and asiminecin. [p4.11.6]While it is not as efficient, they have now modified this method and extended it to the synthesis of the bis-THF acetogenins with asymmetrical cores. [p4.11.7]", "children": [ { "id": "p4.11.1", "order": 44, "type": "text", "bbox": { "l": 314.4, "t": 450.24, "r": 559.68, "b": 355.68 }, "text": "⁷³", "attrs": { "inline": true, "text_offset": 188, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.11.2", "order": 45, "type": "text", "bbox": { "l": 314.4, "t": 450.24, "r": 559.68, "b": 355.68 }, "text": "γ", "attrs": { "inline": true, "text_offset": 206, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.11.3", "order": 46, "type": "text", "bbox": { "l": 314.4, "t": 450.24, "r": 559.68, "b": 355.68 }, "text": "γ'", "attrs": { "inline": true, "text_offset": 217, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.11.4", "order": 47, "type": "text", "bbox": { "l": 314.4, "t": 450.24, "r": 559.68, "b": 355.68 }, "text": "α", "attrs": { "inline": true, "text_offset": 268, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.11.5", "order": 48, "type": "text", "bbox": { "l": 314.4, "t": 450.24, "r": 559.68, "b": 355.68 }, "text": "γ", "attrs": { "inline": true, "text_offset": 282, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.11.6", "order": 49, "type": "text", "bbox": { "l": 314.4, "t": 450.24, "r": 559.68, "b": 355.68 }, "text": "^{74,75}", "attrs": { "inline": true, "text_offset": 392, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.11.7", "order": 50, "type": "text", "bbox": { "l": 314.4, "t": 450.24, "r": 559.68, "b": 355.68 }, "text": "⁷⁶", "attrs": { "inline": true, "text_offset": 551, "text_span": 9, "bbox_estimated": true } } ] }, { "id": "p4.12", "order": 51, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "Several elegant attempts have been directed toward the synthesis of core synthons that could be utilized to produce biologically active natural and nonnatural analogues of the acetogenins. This can be seen in the work of Sasaki et al.,[p4.12.1] Towne and McDonald,[p4.12.2] Figadère et al.,[p4.12.3] Ruan et al.,[p4.12.4] Li et al.,[p4.12.5] Gesson et al.,[p4.12.6] Koret et al.,[p4.12.7] Seepersaud et al.,[p4.12.8] Zhang et al.,[p4.12.9] and Zanardi et al.[p4.12.10] The semisynthetic work of Ye et al.[p4.12.11] has shown that certain chlorinated derivatives of the natural acetogenins lose activity; this suggests that the C-4 hydroxyl and the THF flanking hydroxyls may be involved in some electron-donating hydrogen-bonding interactions at the target site or in the membranes. We anticipate that nitrogen or sulfur derivatives might enhance or modify the activity, selectivity, and/or the potency of acetogenins. Sasaki et al. have synthesized several bullatacin analogues in order to test their metal-binding ability.[p4.12.12] The implications of their work will be discussed in the following section dealing with mechanism of action.", "children": [ { "id": "p4.12.1", "order": 52, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁷⁷", "attrs": { "inline": true, "text_offset": 235, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.12.2", "order": 53, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁷⁸", "attrs": { "inline": true, "text_offset": 264, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.12.3", "order": 54, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁷⁹", "attrs": { "inline": true, "text_offset": 290, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.12.4", "order": 55, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁸⁰", "attrs": { "inline": true, "text_offset": 312, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.12.5", "order": 56, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁸¹", "attrs": { "inline": true, "text_offset": 332, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.12.6", "order": 57, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁸²", "attrs": { "inline": true, "text_offset": 356, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.12.7", "order": 58, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁸³", "attrs": { "inline": true, "text_offset": 379, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.12.8", "order": 59, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁸⁴", "attrs": { "inline": true, "text_offset": 407, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.12.9", "order": 60, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁸⁵", "attrs": { "inline": true, "text_offset": 430, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.12.10", "order": 61, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁸⁶", "attrs": { "inline": true, "text_offset": 458, "text_span": 10, "bbox_estimated": true } }, { "id": "p4.12.11", "order": 62, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁸⁷", "attrs": { "inline": true, "text_offset": 504, "text_span": 10, "bbox_estimated": true } }, { "id": "p4.12.12", "order": 63, "type": "text", "bbox": { "l": 313.92, "t": 354.72, "r": 559.92, "b": 166.08 }, "text": "⁸⁸", "attrs": { "inline": true, "text_offset": 1024, "text_span": 10, "bbox_estimated": true } } ] }, { "id": "p4.13", "order": 64, "type": "text", "bbox": { "l": 314.4, "t": 164.88, "r": 559.44, "b": 90.24 }, "text": "The following compounds have also been recently synthesized: longifolicin,[p4.13.1] 15-epi-annonin I,[p4.13.2] 4-deoxygigantecin (the first bis nonadjacent THF acetogenin to be synthesized),[p4.13.3] (+)-squamocin K, (+)-5S-hydroxyarviflorin, and (+)-parviflorin,[p4.13.4] (+)-squamostanal-A,[p4.13.5] and ( $ 8R $) and ( $ 8S $)-corossoline.[p4.13.6] The methods employed are diverse, and the reader is encouraged to consult the original papers.", "children": [ { "id": "p4.13.1", "order": 65, "type": "text", "bbox": { "l": 314.4, "t": 164.88, "r": 559.44, "b": 90.24 }, "text": "⁸⁹", "attrs": { "inline": true, "text_offset": 74, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.13.2", "order": 66, "type": "text", "bbox": { "l": 314.4, "t": 164.88, "r": 559.44, "b": 90.24 }, "text": "⁹⁰", "attrs": { "inline": true, "text_offset": 101, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.13.3", "order": 67, "type": "text", "bbox": { "l": 314.4, "t": 164.88, "r": 559.44, "b": 90.24 }, "text": "⁹¹", "attrs": { "inline": true, "text_offset": 190, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.13.4", "order": 68, "type": "text", "bbox": { "l": 314.4, "t": 164.88, "r": 559.44, "b": 90.24 }, "text": "⁹²", "attrs": { "inline": true, "text_offset": 263, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.13.5", "order": 69, "type": "text", "bbox": { "l": 314.4, "t": 164.88, "r": 559.44, "b": 90.24 }, "text": "⁹³", "attrs": { "inline": true, "text_offset": 292, "text_span": 9, "bbox_estimated": true } }, { "id": "p4.13.6", "order": 70, "type": "text", "bbox": { "l": 314.4, "t": 164.88, "r": 559.44, "b": 90.24 }, "text": "⁹⁴", "attrs": { "inline": true, "text_offset": 342, "text_span": 9, "bbox_estimated": true } } ] }, { "id": "p4.14", "order": 71, "type": "heading", "bbox": { "l": 315.12, "t": 82.08, "r": 418.8, "b": 71.04 }, "text": "Mechanism of Action", "attrs": { "block_label": "paragraph_title" }, "level": 3 }, { "id": "p4.15", "order": 72, "type": "text", "bbox": { "l": 313.92, "t": 65.76, "r": 559.2, "b": 33.36 }, "text": "The acetogenins are known to be very potent cytotoxic compounds. Demonstrated targets were previously discussed as the reduced nicotinamide adenine dinucleotide" } ], "excluded_furniture": { "first": [], "last": [] } }