Azadirone and its Natural Analogues. This group consists of limonoids in which all rings of the
triterpenoid skeleton remain intact (Table 4). Characteristics features of this group are
presence of oxygen functions at C-3 and C-7. Following the isolation of azadirone (42) from
neem oil,88 nimocin(43) was found in neem leaves.l34 It was suggested that nimocin could be
biogenetic precursor of other benzoyl derivatives of neem meliacins. 6-Hydroxy azadirone and
its 1,2-dihydro derivatives have been named as nimocinol(45) and isomeldenin(48)
respectively. So one has additional names for the related congeners, 46 and 47. While
meldenin diol (46) was found in fresh green leaves, isomeldenin (48) was reported from fallen
yellow ones 108 The compound 49 is the novel homologue of azadirone isolated from neem. It
is the first instance of the occurrence of a ring A carbocylic limonoid homologue. On the basis of
2D IH-13C NMR and NOE studies it has been assigned the structure, 4 α, 6 α -dihydroxy-A-
homoazadirone28 7-Acetylneotrichilenone (50) is another novel constituent whose structure
was confirmed by X-ray analysis72:, The stereochemistry of C/D ring fusion was shown to be
cis by NOE experiments. Irradiation on 18-H gave the signals of 22-H, 14-H and 16-H,
suggesting that 14-H, 18-H and furan ring were on the same side in the α - position. This could
have arisen by the stereo specific cleavage of nimbinin (60) and subsequent oxidation to 15-
one.
triterpenoid skeleton remain intact (Table 4). Characteristics features of this group are
presence of oxygen functions at C-3 and C-7. Following the isolation of azadirone (42) from
neem oil,88 nimocin(43) was found in neem leaves.l34 It was suggested that nimocin could be
biogenetic precursor of other benzoyl derivatives of neem meliacins. 6-Hydroxy azadirone and
its 1,2-dihydro derivatives have been named as nimocinol(45) and isomeldenin(48)
respectively. So one has additional names for the related congeners, 46 and 47. While
meldenin diol (46) was found in fresh green leaves, isomeldenin (48) was reported from fallen
yellow ones 108 The compound 49 is the novel homologue of azadirone isolated from neem. It
is the first instance of the occurrence of a ring A carbocylic limonoid homologue. On the basis of
2D IH-13C NMR and NOE studies it has been assigned the structure, 4 α, 6 α -dihydroxy-A-
homoazadirone28 7-Acetylneotrichilenone (50) is another novel constituent whose structure
was confirmed by X-ray analysis72:, The stereochemistry of C/D ring fusion was shown to be
cis by NOE experiments. Irradiation on 18-H gave the signals of 22-H, 14-H and 16-H,
suggesting that 14-H, 18-H and furan ring were on the same side in the α - position. This could
have arisen by the stereo specific cleavage of nimbinin (60) and subsequent oxidation to 15-
one.
| Table 4. Limonoids of azadirone group |
Stru- Name Substituents Molecular m.p. Isolated Ref.
ture R1 R2 R3 Formula Weight (*C) from No.
No.
51. Azadiradione Ac H β-Furan C28H34O5 450 168 Fruit/oil 88
52. 17-Epi-Azadiradione Ac β-Furan H C28H34O5 450 205 Seed/fruit 69
53. 17- β-Hydroxy
Azadiradione Ac OH β-Furan C28H34O6 466 177 See/Fruit 69
54. 17-α-Hydroxy
Azadiradione Ac β-Furan OH C28H34O6 466 Fruit pulp 128
55. Nimbocinol H H Furan C26H32O4 408 161 Ripe fruit 136
56. 17-Epinimbocinol H β-Furan H C26H32O4 408 49
57. 17 β-Hydroxy
nimbocinol H H β-Furan C26H32O5 424 Fruit/seed 89
58. 7-Benzoyl nimbocinol Bz H β-Furan C33H36O5 512 Amor. Seed/fruit 72
59. Nimolicinoic acid Ac H C26H34O6 442 94 Fruit 141
60. Nimbinin (Nn) Ac 1 - C28H34O6 466 203 Oil 88,105,126
61. 1- α-Methoxy-
1,2-dihydroNn Ac 1 α-Ome-2H - C29H38O7 498 235-6 Dried seeds 72
62. 1 β-2 β-EproxyNn Ac 1β,2 β-0 - C28H34O7 482.6 110-111 Dried seeds 72
63. 7-Deacetyl-7-benzoyINn Bz 1 - C33H36O6 528.3 Amorph. - 72
64. DihydroNn Ac H,H - C28H36O6 468 165
ture R1 R2 R3 Formula Weight (*C) from No.
No.
51. Azadiradione Ac H β-Furan C28H34O5 450 168 Fruit/oil 88
52. 17-Epi-Azadiradione Ac β-Furan H C28H34O5 450 205 Seed/fruit 69
53. 17- β-Hydroxy
Azadiradione Ac OH β-Furan C28H34O6 466 177 See/Fruit 69
54. 17-α-Hydroxy
Azadiradione Ac β-Furan OH C28H34O6 466 Fruit pulp 128
55. Nimbocinol H H Furan C26H32O4 408 161 Ripe fruit 136
56. 17-Epinimbocinol H β-Furan H C26H32O4 408 49
57. 17 β-Hydroxy
nimbocinol H H β-Furan C26H32O5 424 Fruit/seed 89
58. 7-Benzoyl nimbocinol Bz H β-Furan C33H36O5 512 Amor. Seed/fruit 72
59. Nimolicinoic acid Ac H C26H34O6 442 94 Fruit 141
60. Nimbinin (Nn) Ac 1 - C28H34O6 466 203 Oil 88,105,126
61. 1- α-Methoxy-
1,2-dihydroNn Ac 1 α-Ome-2H - C29H38O7 498 235-6 Dried seeds 72
62. 1 β-2 β-EproxyNn Ac 1β,2 β-0 - C28H34O7 482.6 110-111 Dried seeds 72
63. 7-Deacetyl-7-benzoyINn Bz 1 - C33H36O6 528.3 Amorph. - 72
64. DihydroNn Ac H,H - C28H36O6 468 165
Azadiradione(51) and its derivatives (52-64, Table 4) constitute a major group of limonoids wherein the tetracyclic structural framework is
intact. The presence of 16-keto group could cause C-17 epimerisation during biogenesis and one has examples of the C-17 epimers
isolated from neem such as 51 and 52, 17 β 3/ α -hydroxy azadiradiones (53 and 54) and nimbocinols (55 and 56). A comparison of 'H
spectra of the first pair of epimers revealed the significant differences in the chemical shifts of H-18, H-21, H-22 and H-23, wherein the furyl
protons have gone up field while H-18 downfield by about 0.2 ppm in 52 as a consequence of epimerisation. Similarly, one could observe
up field shift of C-12 and C-30 when C-14, C-16, C-18 and C-20 were deshielded by 4-6 ppm. The constituents 56-58 are conveniently
renamed as derivatives of nimbocinol (55) and the last one is closely related to nimocin (44). For the same reason, 14-15-
epoxyazadiradione88 is identical with nimbininI05(60), one of the three limonoids first reported by Siddiqui I26. It could arise by the
epoxidation of 51. Subsequently, four more derivatives 61.:64 have been reported from seeds.72 The preponderence of these constituents
are
Table 5. Limonoids with oxidatively expanded ring D-gedium group
Stru- Name Molecular m.p. Isolated form Ref.
ture Formula Weight (*C) No.
No.
65. Gedunin C28H36O7 482 220 Fruit/bark 88
66. 7-Desacetyl gedium 440 259-62 Fruit/bark 82
67. 7-Desacetyl-7-benzoyl ged. 544 278 Dried seeds 72
68. Nimolicionol 482.23 270-4 Fresh ripe fruits 129
69. Mahmoodin 526.26 Amorph. Seed oil 147
Clearly suggestive of the potential of neem towards further biogenetic modifications particularly at C-I and C-15.
intact. The presence of 16-keto group could cause C-17 epimerisation during biogenesis and one has examples of the C-17 epimers
isolated from neem such as 51 and 52, 17 β 3/ α -hydroxy azadiradiones (53 and 54) and nimbocinols (55 and 56). A comparison of 'H
spectra of the first pair of epimers revealed the significant differences in the chemical shifts of H-18, H-21, H-22 and H-23, wherein the furyl
protons have gone up field while H-18 downfield by about 0.2 ppm in 52 as a consequence of epimerisation. Similarly, one could observe
up field shift of C-12 and C-30 when C-14, C-16, C-18 and C-20 were deshielded by 4-6 ppm. The constituents 56-58 are conveniently
renamed as derivatives of nimbocinol (55) and the last one is closely related to nimocin (44). For the same reason, 14-15-
epoxyazadiradione88 is identical with nimbininI05(60), one of the three limonoids first reported by Siddiqui I26. It could arise by the
epoxidation of 51. Subsequently, four more derivatives 61.:64 have been reported from seeds.72 The preponderence of these constituents
are
Table 5. Limonoids with oxidatively expanded ring D-gedium group
Stru- Name Molecular m.p. Isolated form Ref.
ture Formula Weight (*C) No.
No.
65. Gedunin C28H36O7 482 220 Fruit/bark 88
66. 7-Desacetyl gedium 440 259-62 Fruit/bark 82
67. 7-Desacetyl-7-benzoyl ged. 544 278 Dried seeds 72
68. Nimolicionol 482.23 270-4 Fresh ripe fruits 129
69. Mahmoodin 526.26 Amorph. Seed oil 147
Clearly suggestive of the potential of neem towards further biogenetic modifications particularly at C-I and C-15.
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