Narcissus and Daffodil

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18 17 HO HO HO N OMe HO Synthesis of galanthamine 317 the phenolic hydroxyl groups was not necessary. The amide modification of the N-methyl part of the substrate, and the successful oxidation in homogeneous conditions, were also important methodological findings. Galanthamine synthesis via N-formylnorbelladine derivative HO NH The logical continuation of the syntheses shown in Figures 12.5 to 12.10 was realised in the improved method of galanthamine synthesis proposed by Szewczyk et al. (1988, 1995) (Figure 12.11). This involved a six-step scheme starting from 4-hydroxyphenethylamine (17) and isovanilline (18) via the Schiff base 79, which was reduced without isolation using NaBH 4 to a secondary amine 80 in 99% yield. The latter, on treatment with ethyl formate, gave the corresponding formamide 81 in 80% yield, which on bromination with bromine in chloroform – methanol mixture (–65 °C) afforded the bromo-formamide 82 (85%). K 3 [Fe(CN) 6 ] oxidation gave the expected benzazepine 83 (21%). The final LiAlH 4 reduction produced a mixture OMe HO HO 79 80 81 N CHO Br OH OMe MeO O Br 82 83 O N N CHO CHO OMe 1+4 Figure 12.11 Synthesis of galanthamine (1) via N-formylnorbelladine derivative (82) (Szewcyzk et al., 1988, 1995).
318 V.N. Bulavka and O.N. Tolkachev of 53% (±)-1 and 31% (±)-4. The total yield of (±)-1 according to this scheme was 7.5%, which exceeded by 3.5 times the results published in the work of Kametani et al. (1969a,b). Taking into account that isovanilline (18) is usually obtained from veratric aldehyde (38) in 61% yield (100% conversion) (Brossi et al., 1967), in this scheme Szewczyk et al. (1988, 1995) used all commercially available compounds. The synthesis seems to be simple in realisation on a preparative scale, but its basic deficiency is the use of the inflammable LiAlH4 . Galanthamine synthesis developed by the Russian group A comparative analysis of the known approaches to galanthamine synthesis has revealed the best route to the production of the key compound containing the carbonyl moiety as the formamido group, shown in Figure 12.11. The failing of the majority of known methods is the low yields obtained. The present authors have used the following strategy in a large-scale approach to its synthesis: the use of cheap and commercially available materials, a minimum number of steps, and the use of synthones with unsubstituted hydroxy groups. We have proposed the synthesis of (±)-1 from 4-hydroxyphenethylamine (17), or its O-alkyl derivatives, and 2-bromo-5-hydroxy-4-methoxy-benzaldehyde (39) (Bulavka, 1993; Bulavka et al., 1990, 1991, 1993, 1994a,b,c, 1999; Bulavka and Tolkachev, 1995) (Figure 12.12). The known methods of parent compound production were modified. Thus, 4-hydroxy- and 4-alkoxyphenethylamines (86, R = H, Me, Et, Pr, PhCH 2 ) were obtained from the corresponding 4-substituted benzaldehydes (84) via substituted 2′-nitrostyrenes (85) through zinc dust reduction in diluted hydrochloric acid or in a mixture of hydrochloric and acetic acids. The method was optimised to produce the expected 4-hydroxy- and 4-alkoxyphenethylamines in 80–98% yields in one operation (Bulavka et al., 1993, 1994a,c), higher yields than in earlier published methods. Primary amines 86 afforded formamides 87 (90–95%) with formic acid. 87 (R = Me) was reduced to N-methylated amine 91 with NaBH 4 – acetic acid (74%) and alternatively with zinc dust and sulphuric acid in tetrahydrofouran (67%) (Bulavka, 1993; Bulavka et al., 1994c). The alternative method of N-methyl- 4-methoxyphenethylamine and N-methyl-4-hydroxyphenethylamine production starting from 4-methoxyacetophenone (88) via N-methyl-4-methoxyphenylthioacetamide (89) was also studied. The Willgerodt-Kindler reaction of 88 and MeNH 2 (160–170 °C in ampoules) gave a complex mixture of products, from which 89 (10.4%) was isolated together with the by-product N-methyl-4-methoxyphenylacetamide (21.9%). The method was modified as follows: interaction of 4-methoxyacetophenone (88) with methylamine in the presence of dehydrating agents gave the expected Schiff base 90 in 77% yield, which was then transformed to desired thioamide 89 in 21.5% yield. The reaction of 88 with methylamine hydrochloride and sulphur in dimethylformamide (100 °C, sodium acetate, or 60– 70 °C, 4-toluenesulfonic acid – Et 3 N) gave 89 in 57–58% yields. The reaction of 88 with MeNHCHO and sulphur (170–180 °C) afforded the expected 89 in 30–35% yield. Subsequent reduction of 89 with zinc dust and hydrochloric acid afforded N-methyl-4-methoxyphenethylamine (91) (91%), which was demethylated with hydrochloric acid at 170 °C to N-methyl-4-hydroxyphenethylamine (92) (98%) (Bulavka, 1993; Bulavka et al., 1999).
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Narcissus and Daffodil
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Narcissus and Daffodil The genus Na
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Contents Preface to the series vii
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Preface to the series There is incr
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Preface My interest in flower-bulb
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Acknowledgements I would like to th
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Gordon R. Hanks Crop and Weed Scien
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Figures 1.1 The effect of bulb stor
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Figures/Plates xvii 7.8 Accumulatio
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Figures/Plates of different segment
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2 G.R. Hanks Information about the
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4 G.R. Hanks (1999), and the polysa
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3 2 4 1 1 3 2 4 5 Flowering in 1976
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8 G.R. Hanks Figure 1.6 Diagrammati
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10 G.R. Hanks (Rees, 1969). When fl
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12 G.R. Hanks Figure 1.8 The relati
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14 G.R. Hanks root system of commer
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16 G.R. Hanks Cremer, M.C., Beijer,
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18 G.R. Hanks Roh, S.M. and Lee, J.
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20 A.C. Dweck Figure 2.1 The narcis
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22 A.C. Dweck Julians Hertfordshire
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24 A.C. Dweck Herefordshire, if daf
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26 A.C. Dweck the basis of an ancie
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28 A.C. Dweck Britten, J. and Holla
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3 Classification of the genus Narci
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(1) (2) (3)
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34 B. Mathew d. Section Jonquillae
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36 B. Mathew N. cyclamineus DC. Flo
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38 B. Mathew 1c. Section Ganymedes
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40 B. Mathew umbel, fragrant; peria
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42 B. Mathew recognition whatsoever
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44 B. Mathew Note: N. elegans shows
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46 B. Mathew ssp. praecox Gatt. and
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(1) (2) (3) (4)
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50 B. Mathew Table 3.1 Horticultura
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52 B. Mathew RHS (1958) The Classif
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54 G.R. Hanks grown for galanthamin
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56 G.R. Hanks such as drying stores
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Table 4.4 Areas of Narcissus cultiv
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60 G.R. Hanks Following planting in
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62 G.R. Hanks lost, resulting in th
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64 G.R. Hanks pathogen-tested nucle
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Figure 4.1 Mean monthly weather dat
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68 G.R. Hanks (as well as natural e
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70 G.R. Hanks compaction and its ef
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72 G.R. Hanks bulbs with base rot)
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74 G.R. Hanks Figure 4.3 Modern fro
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76 G.R. Hanks caution. Higher rates
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78 G.R. Hanks can also be prevented
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80 G.R. Hanks Figure 4.4 A typical
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82 G.R. Hanks Planting date The pra
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84 G.R. Hanks Hanks and Jones, 1986
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86 G.R. Hanks On sloping sites, gro
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88 G.R. Hanks Insecticide and nemat
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90 G.R. Hanks bulb growth, especial
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92 G.R. Hanks Figure 4.7 Changes in
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94 G.R. Hanks methods have been tes
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96 G.R. Hanks the boxes, exiting at
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98 G.R. Hanks usually collected in
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100 G.R. Hanks respond to ethylene
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102 G.R. Hanks using thiabendazole
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104 G.R. Hanks required for the eff
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106 G.R. Hanks and cross-cutting, s
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108 G.R. Hanks In practice, moulds
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110 G.R. Hanks that, with enterpris
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112 G.R. Hanks Balatková, V., Tupy
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114 G.R. Hanks (Narcissus pseudonar
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116 G.R. Hanks Flint, G.J. (1983) E
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118 G.R. Hanks Hanks, G.R. and Rees
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120 G.R. Hanks Khatib, K. al (1996)
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122 G.R. Hanks Luyten, I. (1935) Ve
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124 G.R. Hanks O’Neill, T.M., Man
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126 G.R. Hanks Ruamrungsri, S., Rua
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128 G.R. Hanks Thompson, P.A. (1977
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130 G.R. Hanks Williams, M. (1996)
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132 J.B. Briggs Table 5.1 Typical g
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134 J.B. Briggs Table 5.3 Actual gr
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136 J.B. Briggs Table 5.4 Actual co
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138 J.B. Briggs Table 5.5 Capital c
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140 J.B. Briggs ADAS (1987a) Narcis
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142 J. Bastida and F. Viladomat Fig
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Table 6.1 Narcissus alkaloid struct
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Table 6.1b Continued Alkaloid name
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Table 6.1d Tazettine type O O R1 R2
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Table 6.1f Continued MeO Alkaloid n
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Table 6.2 Continued Species* Alkalo
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162 J. Bastida and F. Viladomat Tab
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Table 6.3 Continued Alkaloid* Formu
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Table 6.3 Continued Alkaloid* Formu
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176 J. Bastida and F. Viladomat Tab
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178 J. Bastida and F. Viladomat Cri
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180 J. Bastida and F. Viladomat It
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184 J. Bastida and F. Viladomat is
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186 J. Bastida and F. Viladomat and
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Table 6.4 Continued Alkaloid Activi
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196 J. Bastida and F. Viladomat tac
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198 J. Bastida and F. Viladomat Ang
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200 J. Bastida and F. Viladomat Boi
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202 J. Bastida and F. Viladomat lyc
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204 J. Bastida and F. Viladomat Fug
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206 J. Bastida and F. Viladomat Han
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208 J. Bastida and F. Viladomat Kin
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210 J. Bastida and F. Viladomat of
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212 J. Bastida and F. Viladomat Sp
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214 J. Bastida and F. Viladomat Wil
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216 C. Codina and, consequently, hi
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218 C. Codina easily lost on transf
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220 C. Codina they might be more su
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222 C. Codina µ g/g FW µ g/g FW 3
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224 C. Codina Kinetin As observed i
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226 C. Codina Table 7.3 Total produ
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228 C. Codina Accumulation of alkal
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230 C. Codina Accumulation of alkal
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232 C. Codina Effect on growth and
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234 C. Codina mg/g DW mg/g DW 0.90
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236 C. Codina mg/g DW mg/g DW 1.4 1
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238 C. Codina mg/g DW mg/g DW 1.5 1
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240 C. Codina Hanks, G.R. and Jones
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8 Narcissus and other Amaryllidacea
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244 O.A. Cherkasov and O.N. Tolkach
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9 Studies on galanthamine extractio
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258 M. Kreh Table 9.1 Results of ga
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260 M. Kreh relation to the qualita
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262 M. Kreh Figure 9.3 Galanthamine
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264 M. Kreh 2.0 flower 2 1 3 4 0 10
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Page 291 and 292: H O MeO O MeO H H HO H (1) (3) + 2
Page 293 and 294: 272 M. Kreh Gorinova, N.I., Atanass
Page 295 and 296: 274 R.M. Moraes (Katz and Taneck, 1
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Page 307 and 308: 11 Extraction and quantitative anal
Page 309 and 310: 288 N.P.D. Nanayakkara and J.K. Bas
Page 317 and 318: Table 11.1 GC and HPLC procedures f
Page 319 and 320: Table 11.1 Continued References Det
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Page 353 and 354: 13 Compounds from the genus Narciss
Page 355 and 356: 334 D. Brown with neostigmine the a
Page 357 and 358: 336 D. Brown Absorption Galanthamin
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Page 363 and 364: 342 D. Brown cortex and hippocampus
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Page 367 and 368: 346 D. Brown Galanthamine causes br
Page 369 and 370: 348 D. Brown (1994) go on to mentio
Page 371 and 372: 350 D. Brown (Punto Toro and Rift V
Page 373 and 374: 352 D. Brown Furusawa, E., Lum, M.K
Page 375 and 376: 354 D. Brown Snorrason, E. and Stef
Page 377 and 378: 356 D. Brown examination of a brain
Page 379 and 380: 358 D. Brown A successful cholinerg
Page 381 and 382: Table 14.2 Summary of human trials
Page 383 and 384: 362 D. Brown statistically signific
Page 385 and 386: 364 D. Brown ( Jann, 1998); see Tab
Page 387 and 388: 366 D. Brown REFERENCES Bartus, B.T
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368 D. Brown Wilcock, G.K., Scott,
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370 K. Ingkaninan, H. Irth and R. V
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16 Narcissus lectins Els J.M. Van D
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382 E.J.M. Van Damme and W.J. Peuma
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17 Narcissus in perfumery HISTORY C
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394 C. Remy Figure 17.2 Flower coll
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Figure 17.3 Narcissus flowers sprea
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398 C. Remy CONCLUSION The use of n
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400 C.G. Julian and P.W. Bowers Fig
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406 C.G. Julian and P.W. Bowers sym
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19 Review of pharmaceutical patents
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410 J.R. Murray to certain RNA viru
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412 J.R. Murray occurs in a two-pha
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414 J.R. Murray cognitive function
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416 J.R. Murray given at a time bet
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418 J.R. Murray Hofmannor, D., Mosc
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420 Index Backache, 403 Bacterial d
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422 Index Divisions (classification
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424 Index Leaf numbers, 11 Leaf sco
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426 Index Poet’s cultivars, 34 Po
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428 Index Subgenus (taxonomy); Ajax
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