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Iran’s chief nuclear negotiator, a relative moderate who struggled fiercely against the uncompromising agenda of President Mahmoud Ahmadinejad, has resigned his high-profile post, government officials announced Saturday.

The resignation of Ali Larijani dealt a major setback to Iranian moderates trying to forge a compromise over Iran’s pursuit of nuclear technology, which is strongly opposed by the West.

For two years, Larijani had been secretary of the powerful Supreme National Security Council, which advises the highest levels of the Iranian government on key matters of state. His withdrawal from the scene “may make negotiations even more problematic than in recent months,” said Patrick Cronin, a nuclear non-proliferation expert at the International Institute for Strategic Studies, a British think tank.

Larijani, scion of a powerful clerical family and a confidant to Supreme Leader Ayatollah Ali Khamenei, is said to oppose Iran’s isolation over its insistence on enriching uranium. Insiders said he advocated cutting a deal with the West to end the crisis, which has led to two sets of economic sanctions against Iran.

Larijani was often at odds with Ahmadinejad, who refused to tone down his rhetoric or steer a more moderate course on the nation’s nuclear ambitions.

“The difference between Ali Larijani and President Ahmadinejad was on the cost of the nuclear issue,” said an adviser to Larijani who spoke on condition of anonymity. “Ahmadinejad insists on not any inch of compromise.”

Word of Larijani’s resignation came a few days after Russian President Vladimir Putin arrived in Tehran and proposed a deal to end the nuclear stalemate, and just before Larijani was to have discussed the issue with European Union foreign policy chief Javier Solana.

“We will consider what you said and your proposal,” Khamenei reportedly told Putin, according to the official IRNA news agency, before adding: “We are determined to satisfy the needs of the country in nuclear energy, and it is for this that we take seriously the question of enrichment.”

Analysts said the resignation probably signified that Iran’s leadership had opted to reject Putin’s proposal, which many observers say was a deal in which Iran would halt its uranium-enrichment program in exchange for concessions from the West.

“Mr. Ali Larijani believed in a sort of compromise on uranium enrichment, but President Ahmadinejad thinks that Iran should go ahead with the current uranium enrichment and current nuclear policy,” said Sadegh Zibakalam, a professor of political science at Tehran University. “Therefore, Mr. Ali Larijani had no option but to resign.”

Reacting to the resignation, White House spokeswoman Eryn Witcher said, “We seek a diplomatic solution to the issue of Iran’s nuclear program and hope that whomever has this position will help lead Iran down a path of compliance with their UN Security Council obligations.”

Since taking up his post more than two years ago, Larijani had repeatedly tried to tender his resignation in frustration over Ahmadinejad’s harsh rhetoric.

“Larijani had resigned several times, and President Mahmoud Ahmadinejad finally accepted his resignation,” government spokesman Gholam-Hussein Elham said Saturday, IRNA reported.

Elham played down the resignation, saying that Iran’s nuclear policies would not change and that Larijani resigned for personal reasons to pursue other political activities. But one former adviser to the Iranian government on the nuclear issue said that “the gap between him and Ahmadinejad had reached a point that he simply had to resign.”