Two New Eremophilane‐Type Sesquiterpenoids from the Rhizomes of Ligularia veitchiana (Hemsl.) Greenm

Two new eremophilane‐type sesquiterpenoids eremophil‐6‐en‐11‐ol ( 1 ) and (7α,9α,10α)‐9,10‐epoxy‐eremophilan‐11‐ol ( 2 ), together with a known eremophilane‐type (6α,8α)‐6,8‐dihydroxyeremophil‐7(11)‐en‐12‐oic acid 12,8‐lactone ( 3 ) were isolated from the rhizomes of Ligularia veitchiana. The structures of 1 and 2 were established by spectral analysis including ¹H‐ and ¹³C‐NMR, HSQC, HMBC, and HR‐ESI‐MS data. The compounds 1 and 3 were assessed against lung‐cancer (A549) and stomach‐cancer (BCG823) cell lines by the MTT method. The results showed that 1 exhibited significant inhibiting activities on the growth of these cancer cells with IC₅₀ values between 1–100 μg/ml, whereas compound 3 had no effect on the same cell lines.     

Aza‐nido‐dodecaboranes and ‐borates from Aza‐closo‐dodecaboranes by the Addition of Neutral or Anionic Bases: Mechanism

The addition of neutral (L = py, NEt₃, NHEt₂, NH₂tBu) and anionic Lewis bases (X^‐ = OH^‐, Br^‐, N₃^‐, Me^‐, NHBu ^‐, NHtBu^‐, [FeCp(CO)₂]^‐) to aza‐closo‐dodecaboranes RNB₁₁H₁₁ ( 1 ) or to derivatives thereof with boron bound non‐hydrogen ligands yields nido‐clusters RNB₁₁H₁₁L or [RNB₁₁H₁₁X]^‐ or derivatives thereof, respectively, the non‐planar pentagonal aperture N—B4—B9—B8—B5 of which hosts a B8—B9 hydrogen bridge. The base is either bound to B8 ( 3 )or B4 ( 5 )or B2( 7 ). The structures of these adducts are concluded from ¹H and ¹¹B NMR including 2D‐NMR spectra, and in the case of MeNB₁₁H₁₁(NHEt₂) (type 3 ) also by a crystal structure analysis. With two of the adducts MeNB₁₁H₁₁L (L = py, NHEt₂), isomers of the type 3 , 5 , and 7 , and with two of the adducts, MeNB₁₁H₁₁(NH₂tBu) and {MeNB₁₁H₁₁[FeCp(CO)₂]}^‐, isomers of the type 3 and 7 could be identified. The position of boron‐bound ligands during the addition of bases to 1 shows, that only vertices of the ortho‐belt of 1 are involved in the opening process. A mechanism is made plausible that starts by the attack of the base at B2 of 1 and opening of the N‐B2 bond, denoted as a [3c, 1c]‐collocation, to give 2 with an endo‐H atom, whose migration into an adjacent bridge position and opening of a second B—N bond, denoted as a [3c, 2c]‐translocation, gives 3 ; this isomer can be transformed into 7 by a sequence of [3c, 2c]‐translocations via the isomers 4 , 5 , and 6 . The chiral type 3 species MeNB₁₁H₁₁L with L = NHEt₂, NH₂tBu undergo a rapid enantiomerization, for whose mechanism the exchange of the bridging and the amine‐H atom has been made plausible.     

Lignans from the Bark of Magnolia kobus

The Et₂O‐soluble fraction from the bark of Magnolia kobus led to the isolation of two new lignans, (+)‐(7α,7′α,8α,8′α)‐3′,4,4′,5,5′‐pentamethoxy‐7,9′: 7′,9‐diepoxylignan‐3‐ol ( 1 ) and (+)‐(7α,7′α,8α,8′α)‐4,5‐dimethoxy‐3′,4′‐(methylenedioxy)‐7,9′: 7′,9‐diepoxylignan‐3‐ol ( 2 ), along with five known lignans 3 – 7 . Their structures were established on the basis of various spectroscopic analyses including 1D‐ (¹H, ¹³C, and DEPT) and 2D‐NMR (COSY, NOESY, HMQC, and HMBC) and by comparison of their spectral data with those of related compounds.     

华泽兰的七个新的倍半萜

Seven new sesquiterpenoids, namely eupatochinilides Ⅰ-Ⅶ （1-7）, together with eight known compounds, euponin （8）, mollisorin A （9）, niveusin B （10）, 8β-（4＇-acetoxy-tiglyloxy）-3β-hydroxy-6Hβ,7Hα-germacra-1（10）E,4E,11（13）-trien-6,12-olide （11）, eupalinifide B （12）, 8β-（4＇-hydroxytigloyloxy）-5-desoxy-8-desacyleuparotin （13）, 3-deacetyeupalinin A （14）, and 15-hydroxyleptocarpin （15）, were isolated from the ethanolic extract of the whole plant of Eupatorium chinense L. Their structures and stereochemistry were established by spectroscopic methods and GIAO based ^13C NMR chemical shift calculations.     

Norditerpenoid alkaloids from <Emphasis Type="Italic">Aconitum septentrionale K</Emphasis>.

Two new alkaloids, Septonine (C₃₅H₄₄N₂O₉) and Septontrionine (C₂₅H₃₉NO₆) were isolated from the roots of Aconitum septentrionale K. According to the ¹H and ¹³C NMR, IR, and mass spectra, Septonin and Septontrionin were assigned the structures of 20-ethyl-7-hydroxy-1α,14α,16β-trimethoxy-6-oxo-17(7→8)abeoaconitan-4-ylmethyl 2-(2,5-dioxopyrrolidin-l-yl)benzoate and 20-ethyl-7-hydroxy-1α,14α,16β-trimethoxy-4-methoxymethyl-17(7→8)abeoaconitan-6-one, respectively.     

Conformations of the Ten-membered Ring in 5, 10-Secosteroids. III: (Z)-3β- and (Z)-3α-Hydroxy-5, 10-seco-1 (10)-cholesten-5-one Esters and (Z)-5, 10-seco-1 (10)-Cholestene-3, 5-dione

(Z)-3β-Acetoxy- and (Z)-3 α-acetoxy-5, 10-seco-1 (10)-cholesten-5-one ( 6a ) and ( 7a ) were synthesized by fragmentation of 3β-acetoxy-5α-cholestan-5-ol ( 1 ) and 3α-acetoxy-5β-cholestan-5-ol ( 2 ), respectively, using in both cases the hypoiodite reaction (the lead tetraacetate/iodine version). The 3β-acetate 6a was further transformed, via the 3β-alcohol 6d to the corresponding (Z)-3β-p-bromobenzoate ester 6b and to (Z)-5, 10-seco-1 (10)-cholestene-3, 5-dione ( 8 ) (also obtainable from the 3α-acetate 7a ). The ¹H-and ¹³C-NMR. spectra showed that the (Z)-unsaturated 10-membered ring in all three compounds ( 6a , 7a and 8 ) exists in toluene, in only one conformation of type C ₁, the same as that of the (Z)-3β-p-bromobenzoate 6b in the solid state found by X-ray analysis. The unfavourable relative spatial factors (interdistance and mutual orientation) of the active centres in conformations of type C ₁ are responsible for the absence of intramolecular cyclizations in the (Z)-ketoesters 6 and 7 ( a and c ).     

Comprehensive 1H and 13C NMR assignment of 13 protobassic acid saponins

This study aimed to carry out complete ¹H and ¹³C NMR assignment of 13 protobassic acid saponins, including arganins A–C ( 1 – 3 ) and F ( 4 ), butyrosides B–D ( 5 – 7 ), tieghemelin ( 8 ), 3′-O-glucosyl-arganin C ( 9 ), Mi-saponins A–C ( 10 – 12 ), and mimusopsin ( 13 ), recorded in methanol-d₄. This was accomplished by the analysis of high-resolution one-dimensional (1D) NMR (¹H and ¹³C), two-dimensional (2D) NMR (¹H–¹H COSY, HSQC, and HMBC), and selectively excited 1D TOCSY spectra. Before this study, ¹H and ¹³C NMR data of arganins A–C ( 1 – 3 ) and F ( 4 ) were partially assigned. Our effort leads to their complete assignment, especially the glycon residue, and revises some reported data. Some revisions of the ¹H and ¹³C NMR data in the glycon part of butyroside C ( 6 ), tieghemelin ( 8 ), Mi-saponin A ( 10 ), and mimusopsin ( 13 ) were made. Those data of butyrosides B and D ( 5 & 7 ) and Mi-saponin B ( 11 ), which had not been recorded in methanol-d₄, are provided. In addition, the ¹H and ¹³C NMR data of Mi-saponin C ( 12 ) are reported for the first time. These data, being recorded in methanol-d₄, should be more friendly for use as a reference for identifying the related triterpenoid saponins.     

Nucleosides: Synthesis of Some New Naphthimidazole Ribonucleosides as Potential Antibacterial Agents

Reaction of 2-trifluoromethyl- or 2-cyanonaphth[2,3-d] imidazole (1 or 2) with 1-O-acetyl-2,3,5-tri-O- benzoyl-β-D-ribofuranose (3), using the triflate or fusion method afforded 2-trifluoromethyl-1-(2,3,5-tri- O-benzoyl-α-D- or -β-D-ribofuranosyl)naphth[2,3-d]imidazole (4 or 6) and 2-cyano-1-(2,3,5-tri-O-benzoyl-α-D- or β-D-ribofuranosyl)naphth[2,3,-d] imidazole (5 or 7), respectively. The products 4 and 5 or 6 and 7 were separated by chromatography on silica gel. Treatment of the blocked nucleosides 4-7 with methanolic NH₃ at 0 °C furnished the deblocked nucleosides 8-11 respectively. Treatment of 10 with 5% NH₃ (aq) at 60 °C gave 11. Structural elucidation is based on elemental analysis, UV, FAB-MS and ¹H NMR spectra. Compounds 4-11 were subjected to antibacteial testing. Compounds 5, 7 and 10 have significant activity against Staphylococous aureus (gram positive) and Esherichia coli (gram negative) bacteria, whereas the other tested compounds showed no significant activity.     

One‐range Addition Theorems for Complete Sets of Modified Exponential Type Orbitals and Noninteger n Slater Functions in Standard Convention

Using the L ‐generalized Laguerre polynomials L ‐GLPs) and φ ‐generalized exponential type orbitals φ ‐GETOs) introduced by the author in standard convention, the one‐ and two‐center onerange addition theorems are established for the complete sets of Ψ^(α*) ‐modified exponential type orbitals (Ψ^(α*) ‐METOs) and noninteger n χ‐Slater type orbitals (χ‐NISTOs), where p_l* = 2l + 2 ‐ α* and α* is the integer (α* = α, ?∞ < α ≤2) or noninteger (α* ≠ α, ?∞ < α* < 3) self‐frictional quantum number. It should be noted that the origin of the L ‐GLPs, φ ‐GETOs and Ψ^(α*) ‐METOs, therefore, of the one‐range addition theorems presented in this work is the Lorentz damping or self‐frictional field produced by the particle itself.     

Complexation of hydroxylated ent-kaurane diterpenoids with boric acid as an aid to the assignment of the 13C NMR spectra

The ¹³C NMR spectra of some hydroxylated ent-kaurane diterpenoids were measured in CDCl₃-Py-d₅ (1:1) solution and also after addition of boric acid. Complexation of ent-3β,18-, ent-7α,15β-, ent-7α,15α-, ent-15β,16β- and ent-16β,17-dihydroxy derivatives with boric acid produced considerable chemical shift changes and marked broadening of the signals of the hydroxy-bearing and neighbouring carbon atoms. This behaviour provides a useful and reliable method for assigning the ¹³C NMR spectra of these compounds.     

New Sesquiterpenoids from Ligularia duciformis

From the whole plants of Ligularia duciformis, four new sesquiterpenoids, 3β‐acetoxy‐6β‐methoxyeremophila‐7(11),9(10)‐dien‐12,8β‐olide ( 1 ), 3β‐acetoxy‐8α‐hydroxy‐6β‐methoxyeremophila‐7(11),9(10)‐dien‐12,8β‐olide ( 2 ), 3β‐acetoxy‐10β‐hydroxy‐6β,8β‐dimethoxyeremophil‐7(11)‐en‐12,8α‐olide ( 3 ), and 3β‐acetoxy‐6β,8β,10β‐trihydroxyeremophil‐7(11)‐en‐12,8α‐olide ( 4 ) were isolated. Their structures were established by high‐field NMR techniques (¹H,¹H‐COSY, ¹³C‐APT, HMQC, HMBC, and NOESY) and HR‐ESI‐MS analysis, together with comparison of the spectroscopic data with those of structurally related compounds. In addition, the cytotoxicity of the new compounds against human hepatic cancer cells Bel‐7402, human pneumonic cancer cells A‐549, and human colonic cancer cells HCT‐8 were evaluated, the new compounds showed no cytotoxicity against the three tumor cells (all IC₅₀ values >200 μM ).     

(6R,9′Z)-Neoxanthin: Synthese,Schmelzverhalten, Spektren und Konformationsberechnungen

(6R,9′Z)-Neoxanthin: Synthesis, Physical Properties, Spectra, and Calculations of Its Conformation in Solution The synthesis of pure and crystalline (9′Z)-neoxanthin ( 6 ) is described. MnO₂ Oxidation of (9Z)-C₁₅-alcohol 7 at room temperature produces a mixture 8/9 of (9Z)- and (9E)-aldehydes. Predominant formation of the required (9Z)-aldehyde 8 is achieved by performing the oxidation at ? 10°. Condensation of 8 with the mono-Li salt of the symmetrical C₁₀-diphosphonate 10 gave the (9Z)-C₂₅-monophosphonate 11 . The Wittig-Horner condensation of 10 with the allenic C₁₅-aldehyde 1b , under selected conditions allows the preparation of pure and crystalline (9′Z)-15,15′-didehydroneoxanthin ( 12 ) and, after subsequent semireduction, of crystalline (15Z,9′Z)-neoxanthin ( 13 ). Thermal isomerisation of a AcOEt solution of 13 at 95° yields preferentially (9′Z)-neoxanthin ( 6 ). Our crystalline sample shows the highest ?-values in the UV/VIS spectra ever recorded. The CD spectra display a pronounced similarity with those of corresponding violaxanthin isomers. In contrast to the (all-E)-isomer 5 , (9′Z)-neoxanthin undergoes very little isomerisation when heated to its melting point. For comparison purposes, a crystalline probe of 6 is also isolated from lawn mowings. Extensive ¹H-and ¹³C-NMR investigations at 600 MHz of a (D₆)benzene solution using 2D-experiments such as COSY, TOCSY, ROESY, HMBC, and HMQC techniques permit the unambiguous assignment of all signals. Force-field calculations of a model system of 6 indicate the presence of several interconverting conformers of the violaxanthin end group, 66% of which possess a pseudoequatorial and 34% a pseudoaxial OH? C(3′). The torsion angle (ω₁) around the C(6′)? C(7′) bond, known to be of prime importance for the shape of the CD spectra, varies with values of 87° for 55% and 263° for 45% of the molecules. Therefore, the molecules clearly display a preference for the ‘syn’-position of the C(7′)?C(8′) bond and the epoxy group. Unexpectedly, the double bonds of C(7′)?C(8′) and C(9′)?C(10′) are not coplanar. The deviation amounts to ± 20°, both in the ‘syn’ - and the ‘anti’-conformation.     

ZUM MECHANISMUS MASSENSPEKTROMETRISCHER FRAGMENTIERUNGSREAKTIONEN BEI A/B-CIS- VERKNüPFTEN 3α-HYDROXYSTEROIDEN MIT UND OHNE 11-KETOGRUPPE

Mass spectra of steroids containing a carbonyl group in position 11 and a 3α-hydroxy group in a cis connected A/B ring system are characterised by very strong [M – 72]⁺· key ions and may therefore be clearly differentiated from the spectra of their isomers. The mechanism of this fragmentation reaction was investigated by deuterium labelling and the DADI technique. The 3α-hydroxy group is eliminated together with the 9α-H atom. Next a hydrogen atom is transferred from the A ring to the B/C/D ring system. This causes the cleavage of the C-3? C-4 bond and expulsion of C atoms 1 to 4 as butadiene. In 3α-hydroxy-5α-androstanes possessing no 11-keto group an analogous [M – 18]⁺. fragment is fromed, followed by the elimination of ethylene originating mostly from C-1 and C-2.     

A finite-difference solution of the Hartree–Fock equations for diatomic molecules

A more general application of the self-consistent field iteration is coupled with a finite-difference Newton–Raphson algorithm to solve the set of coupled second-order integro-differential equations with split boundary conditions which constitutes the Hartree–Fock problem for diatomic molecules. The N orbitals are assumed to be of the form ψ_α = L_α(λ) M_α (μ)e^imα^? (2π)^?1/2, (α = 1, …?, N), where λ, μ, and ? are the usual confocal elliptical coordinates. Requiring the expectation value of the electronic Hamiltonian to be stationary with respect to independent variations of the functions L_α and M_α, subject to constraints of orthonormality, leads to a set of coupled one-dimensional differential equations for the functions L_α and M_α. In the new method a corresponding set of finite-difference equations including the split boundary conditions for each function, as well as the Lagrange multipliers and associated constraints on normalization and orthogonality, are incorporated into a large system of nonlinear algebraic equations which is solved by means of a coupled self-consistent field-generalized Newton–Raphson iteration. As examples, calculations of the (1)^{2 1}Σ and (1) (2pσ_u) ³Σ states of H₂ are presented. The calculated energy for the ¹Σ state of H₂ is 99.985% of the three-dimensional Hartree–Fock limit. The discrepancy is due to the assumed factored form of the orbitals ψ_α, and a generalization of the finite-difference method is suggested to improve the results.     

Reactions of Di(tert‐butyl)diazomethane with Acceptor‐Substituted Ethylenes

Di(tert‐butyl)diazomethane ( 4 ) is a nucleophilic 1,3‐dipole with strong steric hindrance at one terminus. In its reaction with 2,3‐bis(trifluoromethyl)fumaronitrile ((E)‐ BTE ), a highly electrophilic tetra‐acceptor‐substituted ethene, an imino‐substituted cyclopentene 9 is formed as a 1 : 2 product. The open‐chain zwitterion 10 , assumed as intermediate, adds the second molecule of (E)‐ BTE . The ¹⁹F‐ and ¹³C‐NMR spectra allow the structural assignment of two diastereoisomers, 9A and 9B . The zwitterion 10 can also be intercepted by dimethyl 2,3‐dicyanofumarate ( 11 ) and furnishes diastereoisomeric cyclopentenes 12A and 12B ; an X‐ray‐analysis of 12B confirms the ‘mixed’ 1 : 1 : 1 product. Competing is an (E)‐ BTE ‐catalyzed decomposition of 4 to give 2,3,4,4‐tetramethylpent‐1‐ene ( 7 )+N₂; the reaction of (E)‐ BTE with a trace of water appears to be responsible for the chain initiation. The H₂SO₄‐catalyzed decomposition of diazoalkane 4 , indeed, produced the alkene 7 in high yield. The attack on the hindered diazoalkane 4 by 11 is slower than that by (E)‐ BTE ; the zwitterionic intermediate 21 undergoes cyclization and furnishes the tetrasubstituted furan 22 . In fumaronitrile, electrophilicity and steric demand are diminished, and a 1,3‐cycloaddition produces the 4,5‐dihydro‐1H‐pyrazole derivative 25 . The reaction of 4 with dimethyl acetylenedicarboxylate leads to pyrazole 29 +isobutene.     

Synthesis and Conformational Analysis of Macrocyclic Dilactones Mimicking the Pharmacophore of Aplysiatoxin

A small number of macrocyclic dilactones of type 3 , i.e., 9, 10, 11 , and epi‐ 11 , comprising a 3,4‐dihydroxypentanoic acid unit, the pharmacophore of aplysiatoxin, and a conformationally preorganized ω‐hydroxynonanoic acid unit were synthesized. Conformational analysis – based on ²J and ³J NMR coupling constants – of the dihydroxypentanoyl part of these macro‐dilactones indicates the extent to which a conformation induction across the macro‐dilactone ring occurs from the stereogenic centres implemented in the ω‐hydroxynonanoic acid part.     

The Crystal and Molecular Structure of 3-Oxo-17β-acetoxy-Δ4-14α-methyl-8α, 9β, 10α, 13α-estrene

The crystal and molecular structure of 3-oxo-17β-acetoxy-Δ⁴-14α-methyl-8α, 9β, 10α, 13α-estrene, C₂₁H₃₀O₃, has been determined by X-ray diffraction analysis. The crystals belong to the orthorhombic space group P2₁2₁2₁, with the cell dimensions a = 12.093 Å, b = 19.667 Å, c = 7.746 Å; Z = 4. Intensity data were collected at room temperature with an automatic four-circle diffractometer. The structure was solved by direct methods and the parameters were refined by least-squares analysis. All the hydrogen atoms were included in the refinement. The final R value was 0.038 for 1413 observed reflections. The conformation of ring A is intermediate between a half-chair and a 1, 2-diplanar form. The hydrogens at C(9) and C(10) are anti, the B/C ring junction is trans, and rings B and C adopt chair conformations. Ring D is cis fused and is halfway between C₂ and C_s forms.     

Conformational Studies of Marine Polyhalogenated α-Chamigrenes Using Temperature-dependent NMR spectra inverted-chair and twist-boat cyclohexane moieties in the presence of an axial halogen atom at C(8)

α-Chamigren-3-one (+) -8 bearing an axial CI-atom at C(8) exists as a largely dominant conformer with Me—C(5) at the envelope-shaped enone ring pointing away from CI_ax?C(8) at the cyclohexane ring (= B) in the ‘normal’ chair conformation, as shown by ¹H-NMR. In contrast, the α-chamigren-3-ols (+) -9 and (+) -10 , obtained from hydride reduction of (+) -8 , show a temperature-dependent equilibrium of conformers where the major conformers have ring B in the inverted-chair (and twist-boat for (+) -9 ) conformation to avoid repulsions between Me?C(5) and CI_ax–C(8) (Scheme 1). This is in agreement with the conformation of the epoxidation product (+) -12 of (+) -9 where Me–C(5) is pushed away from CI_ax–C(8) in a ring-B chair similar to that of (+) -8 (Scheme 2). Introduction of a pseudoequatorial Br-atom at C(2) of (+) -8 , as in enone (+) -15 (Scheme 3), does not affect the conformation; but a pseudoaxial Br? C(2) experiences repulsive interactions with H_eq–C(7), as shown by the ¹H-NMR data of the isomeric enone (+) -16 where the ‘normal’-chair conformer Cβ -16 is in an equilibrium with the inverted chair conformer ICβ -16 (Scheme 3). These results and the accompanying paper allow a unifying view on the conformational behavior of marine polyhalogenated α-chamigrenes. This view is supported by the acid-induced isomerization of α-chamigrene (+) -9 (inverted chair) to β-chamigrene (+) -17 (‘normal’ chair; Scheme 4), the driving force being the lesser space requirement of CH₂?C(5) than of Me–C(5). This explains why β-chamigrenes are so common in nature.     

Structure elucidation of [1,3]oxazolo[4,5‐e][2,1]benzisoxazole and naphtho[1,2‐d][1,3]‐ and phenanthro[9,10‐d]oxazoles using gradient selected gHMBC,gHMQC and gHMQC‐TOCSY NMR techniques

Structure elucidation of compounds in the benzisoxazole series ( 1 – 6 ) and naphtho[1,2‐d][1,3]‐ ( 7 – 10 ) and phenanthro[9,10‐d][1,3]oxazole ( 11 – 14 ) series was accomplished using extensive 2D NMR spectroscopic studies including ¹H–¹H COSY, long‐ range ¹H–¹H COSY, ¹H–¹³C COSY, gHMQC, gHMBC and gHMQC‐TOCSY experiments. The distinction between oxazole and isoxazole rings was made on the basis of the magnitude of heteronuclear one‐bond ¹J_{C2, H2} (or ¹J_{C3, H3}) coupling constants. Complete analysis of the ¹H NMR spectra of 11 – 14 was achieved by iterative calculations. Gradient selected gHMQC‐TOCSY spectra of phenanthro[9,10‐d][1,3]oxazoles 11 – 14 were obtained at different mixing times (12, 24, 36, 48 and 80 ms) to identify the spin system where the protons of phenanthrene ring at H‐5, H‐6 and at H‐9 and H‐7 and H‐8 were highly overlapping. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of 2′-amino-17-cyclopropylmethyl-6,7-dehydro-3,14-dihydroxy-4,5α-epoxy-6,7:4′,5′-thiazolomorphinan from naltrexone

Fusion of an azole moiety at C-6 and C-7 of naltrexone ( 1 ) is illustrated by the synthesis of the title compound 8 . Bromination of 3-O-methylnaltrexone led to the 1,7α-dibromo derivative which reacted with thiourea to attach the 2-aminothiazole ring to C-6 and C-7 of naltrexone. After converting the amino and alcohol groups to trimethylsilyl derivatives, the aromatic bromo group was removed by halo-lithium interchange with butyllithium, followed by hydrolysis with water. In the final step of the synthesis, the methyl ether was cleaved by boron tribromide to generate 8 . An alternate synthesis of 8 commenced with 3-O-acetylnaltrexone ( 9 ). Bromination of 9 in acetic acid in the presence of hydrobromic acid produced a mixture of 3-O-acetyl-7α-bromonaltrexone ( 10 ) and 7α-bromonaltrexone ( 11 ), both, as hydrobromides. Reaction of this mixture with thiourea furnished 8 (62% from 1 ). While ¹H and ¹³C chemical shifts of all compounds are reported, those of 11 hydrobromide and 8 dihydrochloride were established unequivocally.